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Morphologic Regions Represent the Sum of Different Gradients\nThe visual boundary between dorsal and ventral skin in at/at mice is reminiscent of other systems in which adjacent compartments enforce a binary choice between alternative patterns of gene expression and cell fate (reviewed in Dahmann and Basler 1999). However, Agouti mRNA in both embryonic and postnatal skin is distributed along a gradient whose dorsal boundary is indistinct and overlaps with two additional gradients recognized by their effects on hair length and histochemical staining for melanocytes. The three gradients are close but not congruent, and it is their proximity that gives rise to the superficial distinction between dorsal and ventral skin of at/at mice. Indeed, slight differences between the regions of transition for pigment-type switching and pigment content give rise to a subtle yellow stripe along the flank (see Figures 1, 2, and 9A). Levels of Agouti mRNA remain high throughout the entire ventrum, but hair pigment content is reduced, giving rise to a cream-colored region in the ventrum that, depending on age and genetic backgrounds, may appear more or less distinct from the yellow flank stripe.\nFigure 9 Model for Acquisition of Dorsoventral Patterning in the Trunk and the Role of Tbx15\n(A) A tricolor pigmentation pattern is generated by the combination of distinct mechanisms that affect distribution of Agouti mRNA and histochemical staining for melanocytes; effects of the latter mechanism by itself are evident in ae/ae mice (see Figure 1). In at/at mice, reduced hair melanocyte activity and high levels of Agouti mRNA in the ventrum lead to a cream color; as melanocyte activity gradually increases towards the dorsum, a lateral stripe is apparent on the flank. The distributions of Agouti mRNA and histochemical staining for melanocytes are both affected by Tbx15 and are externally evident by a widening of the lateral stripe and an increased proportion of total skin occupied by the cream-colored area.\n(B) The lateral yellow stripe in at/at mice lies at the same level as the limb dorsoventral boundary. As described in the text, we propose that distinct dorsoventral compartments in ectoderm of the trunk provide an instructional cue to the mesoderm, leading to expression of Tbx15 in dorsal trunk mesenchyme and acquisition of dorsal dermis character. In the absence of Tbx15, dorsal mesenchyme assumes ventral characteristics instead. Loss of Tbx15 affects dorsoventral transitions of hair length, pigment content, and expression of the ventral-specific Agouti isoform; however, the former two effects are subtle and contribute little, if at all, to the abnormal pigmentation of adult deH/deH mice. Thus, despite the abnormal pattern of dark skin in neonatal deH/deH mice (e.g., Figure 2D), the most obvious feature in adults is dorsal displacement of the “boundary” between black and yellow hair (Figure 9A)."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T7875","span":{"begin":74,"end":80},"obj":"GO:0007601"},{"id":"T7876","span":{"begin":131,"end":135},"obj":"NCBITaxon:10088"},{"id":"T7877","span":{"begin":255,"end":259},"obj":"SO:0000704"},{"id":"T7878","span":{"begin":255,"end":270},"obj":"GO:0010467"},{"id":"T7879","span":{"begin":333,"end":339},"obj":"PR:000004372"},{"id":"T7880","span":{"begin":353,"end":362},"obj":"UBERON:0000922"},{"id":"T7881","span":{"begin":371,"end":376},"obj":"GO:0007567"},{"id":"T7882","span":{"begin":524,"end":528},"obj":"UBERON:0001037"},{"id":"T7883","span":{"begin":567,"end":578},"obj":"CL:0000148"},{"id":"T7884","span":{"begin":743,"end":747},"obj":"NCBITaxon:10088"},{"id":"T7885","span":{"begin":814,"end":821},"obj":"CHEBI:26130"},{"id":"T7886","span":{"begin":841,"end":848},"obj":"CHEBI:26130"},{"id":"T7887","span":{"begin":903,"end":908},"obj":"UBERON:0000180"},{"id":"T7888","span":{"begin":947,"end":953},"obj":"PR:000004372"},{"id":"T7889","span":{"begin":993,"end":1000},"obj":"UBERON:0013235"},{"id":"T7890","span":{"begin":1006,"end":1010},"obj":"UBERON:0001037"},{"id":"T7891","span":{"begin":1011,"end":1018},"obj":"CHEBI:26130"},{"id":"T7892","span":{"begin":1084,"end":1091},"obj":"UBERON:0013235"},{"id":"T7893","span":{"begin":1119,"end":1126},"obj":"SO:0000704"},{"id":"T7894","span":{"begin":1189,"end":1194},"obj":"UBERON:0000180"},{"id":"T7895","span":{"begin":2467,"end":2472},"obj":"PR:000016145"},{"id":"T7896","span":{"begin":2509,"end":2513},"obj":"UBERON:0001037"},{"id":"T7897","span":{"begin":2522,"end":2529},"obj":"CHEBI:26130"},{"id":"T7898","span":{"begin":2543,"end":2553},"obj":"GO:0010467"},{"id":"T7899","span":{"begin":2578,"end":2584},"obj":"PR:000004372"},{"id":"T7900","span":{"begin":2585,"end":2592},"obj":"SO:0001060"},{"id":"T7901","span":{"begin":2703,"end":2708},"obj":"UBERON:0007023"},{"id":"T7902","span":{"begin":2717,"end":2721},"obj":"NCBITaxon:10088"},{"id":"T7903","span":{"begin":2791,"end":2795},"obj":"NCBITaxon:10088"},{"id":"T7904","span":{"begin":2843,"end":2849},"obj":"UBERON:0007023"},{"id":"T7905","span":{"begin":2916,"end":2920},"obj":"UBERON:0001037"}],"text":"Distinct Morphologic Regions Represent the Sum of Different Gradients\nThe visual boundary between dorsal and ventral skin in at/at mice is reminiscent of other systems in which adjacent compartments enforce a binary choice between alternative patterns of gene expression and cell fate (reviewed in Dahmann and Basler 1999). However, Agouti mRNA in both embryonic and postnatal skin is distributed along a gradient whose dorsal boundary is indistinct and overlaps with two additional gradients recognized by their effects on hair length and histochemical staining for melanocytes. The three gradients are close but not congruent, and it is their proximity that gives rise to the superficial distinction between dorsal and ventral skin of at/at mice. Indeed, slight differences between the regions of transition for pigment-type switching and pigment content give rise to a subtle yellow stripe along the flank (see Figures 1, 2, and 9A). Levels of Agouti mRNA remain high throughout the entire ventrum, but hair pigment content is reduced, giving rise to a cream-colored region in the ventrum that, depending on age and genetic backgrounds, may appear more or less distinct from the yellow flank stripe.\nFigure 9 Model for Acquisition of Dorsoventral Patterning in the Trunk and the Role of Tbx15\n(A) A tricolor pigmentation pattern is generated by the combination of distinct mechanisms that affect distribution of Agouti mRNA and histochemical staining for melanocytes; effects of the latter mechanism by itself are evident in ae/ae mice (see Figure 1). In at/at mice, reduced hair melanocyte activity and high levels of Agouti mRNA in the ventrum lead to a cream color; as melanocyte activity gradually increases towards the dorsum, a lateral stripe is apparent on the flank. The distributions of Agouti mRNA and histochemical staining for melanocytes are both affected by Tbx15 and are externally evident by a widening of the lateral stripe and an increased proportion of total skin occupied by the cream-colored area.\n(B) The lateral yellow stripe in at/at mice lies at the same level as the limb dorsoventral boundary. As described in the text, we propose that distinct dorsoventral compartments in ectoderm of the trunk provide an instructional cue to the mesoderm, leading to expression of Tbx15 in dorsal trunk mesenchyme and acquisition of dorsal dermis character. In the absence of Tbx15, dorsal mesenchyme assumes ventral characteristics instead. Loss of Tbx15 affects dorsoventral transitions of hair length, pigment content, and expression of the ventral-specific Agouti isoform; however, the former two effects are subtle and contribute little, if at all, to the abnormal pigmentation of adult deH/deH mice. Thus, despite the abnormal pattern of dark skin in neonatal deH/deH mice (e.g., Figure 2D), the most obvious feature in adults is dorsal displacement of the “boundary” between black and yellow hair (Figure 9A)."}

{"project":"2_test","denotations":[{"id":"14737183-10431194-84903016","span":{"begin":317,"end":321},"obj":"10431194"},{"id":"T72218","span":{"begin":317,"end":321},"obj":"10431194"}],"text":"Distinct Morphologic Regions Represent the Sum of Different Gradients\nThe visual boundary between dorsal and ventral skin in at/at mice is reminiscent of other systems in which adjacent compartments enforce a binary choice between alternative patterns of gene expression and cell fate (reviewed in Dahmann and Basler 1999). However, Agouti mRNA in both embryonic and postnatal skin is distributed along a gradient whose dorsal boundary is indistinct and overlaps with two additional gradients recognized by their effects on hair length and histochemical staining for melanocytes. The three gradients are close but not congruent, and it is their proximity that gives rise to the superficial distinction between dorsal and ventral skin of at/at mice. Indeed, slight differences between the regions of transition for pigment-type switching and pigment content give rise to a subtle yellow stripe along the flank (see Figures 1, 2, and 9A). Levels of Agouti mRNA remain high throughout the entire ventrum, but hair pigment content is reduced, giving rise to a cream-colored region in the ventrum that, depending on age and genetic backgrounds, may appear more or less distinct from the yellow flank stripe.\nFigure 9 Model for Acquisition of Dorsoventral Patterning in the Trunk and the Role of Tbx15\n(A) A tricolor pigmentation pattern is generated by the combination of distinct mechanisms that affect distribution of Agouti mRNA and histochemical staining for melanocytes; effects of the latter mechanism by itself are evident in ae/ae mice (see Figure 1). In at/at mice, reduced hair melanocyte activity and high levels of Agouti mRNA in the ventrum lead to a cream color; as melanocyte activity gradually increases towards the dorsum, a lateral stripe is apparent on the flank. The distributions of Agouti mRNA and histochemical staining for melanocytes are both affected by Tbx15 and are externally evident by a widening of the lateral stripe and an increased proportion of total skin occupied by the cream-colored area.\n(B) The lateral yellow stripe in at/at mice lies at the same level as the limb dorsoventral boundary. As described in the text, we propose that distinct dorsoventral compartments in ectoderm of the trunk provide an instructional cue to the mesoderm, leading to expression of Tbx15 in dorsal trunk mesenchyme and acquisition of dorsal dermis character. In the absence of Tbx15, dorsal mesenchyme assumes ventral characteristics instead. Loss of Tbx15 affects dorsoventral transitions of hair length, pigment content, and expression of the ventral-specific Agouti isoform; however, the former two effects are subtle and contribute little, if at all, to the abnormal pigmentation of adult deH/deH mice. Thus, despite the abnormal pattern of dark skin in neonatal deH/deH mice (e.g., Figure 2D), the most obvious feature in adults is dorsal displacement of the “boundary” between black and yellow hair (Figure 9A)."}

{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T7906","span":{"begin":74,"end":80},"obj":"GO:0007601"},{"id":"T7907","span":{"begin":117,"end":121},"obj":"UBERON_EXT:zone_of_skin_or_skin_of_body"},{"id":"T7908","span":{"begin":131,"end":135},"obj":"NCBITaxon:10088"},{"id":"T7909","span":{"begin":255,"end":259},"obj":"SO_EXT:0000704"},{"id":"T7910","span":{"begin":255,"end":270},"obj":"GO:0010467"},{"id":"T7911","span":{"begin":275,"end":279},"obj":"CL_GO_EXT:cell"},{"id":"T7912","span":{"begin":333,"end":339},"obj":"PR_EXT:000004372"},{"id":"T7913","span":{"begin":340,"end":344},"obj":"CHEBI_SO_EXT:mRNA"},{"id":"T7914","span":{"begin":353,"end":362},"obj":"UBERON:0000922"},{"id":"T7915","span":{"begin":371,"end":376},"obj":"GO:0007567"},{"id":"T7916","span":{"begin":377,"end":381},"obj":"UBERON_EXT:zone_of_skin_or_skin_of_body"},{"id":"T7917","span":{"begin":524,"end":528},"obj":"UBERON:0001037"},{"id":"T7918","span":{"begin":567,"end":578},"obj":"CL:0000148"},{"id":"T7919","span":{"begin":729,"end":733},"obj":"UBERON_EXT:zone_of_skin_or_skin_of_body"},{"id":"T7920","span":{"begin":743,"end":747},"obj":"NCBITaxon:10088"},{"id":"T7921","span":{"begin":814,"end":821},"obj":"CHEBI_EXT:26130"},{"id":"T7922","span":{"begin":841,"end":848},"obj":"CHEBI_EXT:26130"},{"id":"T7923","span":{"begin":903,"end":908},"obj":"UBERON:0000180"},{"id":"T7924","span":{"begin":947,"end":953},"obj":"PR_EXT:000004372"},{"id":"T7925","span":{"begin":954,"end":958},"obj":"CHEBI_SO_EXT:mRNA"},{"id":"T7926","span":{"begin":993,"end":1000},"obj":"UBERON:0013235"},{"id":"T7927","span":{"begin":1006,"end":1010},"obj":"UBERON:0001037"},{"id":"T7928","span":{"begin":1011,"end":1018},"obj":"CHEBI_EXT:26130"},{"id":"T7929","span":{"begin":1084,"end":1091},"obj":"UBERON:0013235"},{"id":"T7930","span":{"begin":1119,"end":1126},"obj":"SO_EXT:0000704"},{"id":"T7931","span":{"begin":1189,"end":1194},"obj":"UBERON:0000180"},{"id":"T7932","span":{"begin":2467,"end":2472},"obj":"PR_EXT:000016145"},{"id":"T7933","span":{"begin":2509,"end":2513},"obj":"UBERON:0001037"},{"id":"T7934","span":{"begin":2522,"end":2529},"obj":"CHEBI_EXT:26130"},{"id":"T7935","span":{"begin":2543,"end":2553},"obj":"GO:0010467"},{"id":"T7936","span":{"begin":2578,"end":2584},"obj":"PR_EXT:000004372"},{"id":"T7937","span":{"begin":2585,"end":2592},"obj":"SO_EXT:0001060"},{"id":"T7938","span":{"begin":2687,"end":2699},"obj":"GO_PATO_EXT:biological_pigmentation_process_or_quality"},{"id":"T7939","span":{"begin":2703,"end":2708},"obj":"UBERON:0007023"},{"id":"T7940","span":{"begin":2717,"end":2721},"obj":"NCBITaxon:10088"},{"id":"T7941","span":{"begin":2766,"end":2770},"obj":"UBERON_EXT:zone_of_skin_or_skin_of_body"},{"id":"T7942","span":{"begin":2774,"end":2782},"obj":"PATO_UBERON_EXT:neonate_or_newborn"},{"id":"T7943","span":{"begin":2791,"end":2795},"obj":"NCBITaxon:10088"},{"id":"T7944","span":{"begin":2843,"end":2849},"obj":"UBERON:0007023"},{"id":"T7945","span":{"begin":2916,"end":2920},"obj":"UBERON:0001037"}],"text":"Distinct Morphologic Regions Represent the Sum of Different Gradients\nThe visual boundary between dorsal and ventral skin in at/at mice is reminiscent of other systems in which adjacent compartments enforce a binary choice between alternative patterns of gene expression and cell fate (reviewed in Dahmann and Basler 1999). However, Agouti mRNA in both embryonic and postnatal skin is distributed along a gradient whose dorsal boundary is indistinct and overlaps with two additional gradients recognized by their effects on hair length and histochemical staining for melanocytes. The three gradients are close but not congruent, and it is their proximity that gives rise to the superficial distinction between dorsal and ventral skin of at/at mice. Indeed, slight differences between the regions of transition for pigment-type switching and pigment content give rise to a subtle yellow stripe along the flank (see Figures 1, 2, and 9A). Levels of Agouti mRNA remain high throughout the entire ventrum, but hair pigment content is reduced, giving rise to a cream-colored region in the ventrum that, depending on age and genetic backgrounds, may appear more or less distinct from the yellow flank stripe.\nFigure 9 Model for Acquisition of Dorsoventral Patterning in the Trunk and the Role of Tbx15\n(A) A tricolor pigmentation pattern is generated by the combination of distinct mechanisms that affect distribution of Agouti mRNA and histochemical staining for melanocytes; effects of the latter mechanism by itself are evident in ae/ae mice (see Figure 1). In at/at mice, reduced hair melanocyte activity and high levels of Agouti mRNA in the ventrum lead to a cream color; as melanocyte activity gradually increases towards the dorsum, a lateral stripe is apparent on the flank. The distributions of Agouti mRNA and histochemical staining for melanocytes are both affected by Tbx15 and are externally evident by a widening of the lateral stripe and an increased proportion of total skin occupied by the cream-colored area.\n(B) The lateral yellow stripe in at/at mice lies at the same level as the limb dorsoventral boundary. As described in the text, we propose that distinct dorsoventral compartments in ectoderm of the trunk provide an instructional cue to the mesoderm, leading to expression of Tbx15 in dorsal trunk mesenchyme and acquisition of dorsal dermis character. In the absence of Tbx15, dorsal mesenchyme assumes ventral characteristics instead. Loss of Tbx15 affects dorsoventral transitions of hair length, pigment content, and expression of the ventral-specific Agouti isoform; however, the former two effects are subtle and contribute little, if at all, to the abnormal pigmentation of adult deH/deH mice. Thus, despite the abnormal pattern of dark skin in neonatal deH/deH mice (e.g., Figure 2D), the most obvious feature in adults is dorsal displacement of the “boundary” between black and yellow hair (Figure 9A)."}