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1.
Elife ; 122023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37877560

RESUMO

During development, much of the enteric nervous system (ENS) arises from the vagal neural crest that emerges from the caudal hindbrain and colonizes the entire gastrointestinal tract. However, a second ENS contribution comes from the sacral neural crest that arises in the caudal neural tube and populates the post-umbilical gut. By coupling single-cell transcriptomics with axial-level-specific lineage tracing in avian embryos, we compared the contributions of embryonic vagal and sacral neural crest cells to the chick ENS and the associated peripheral ganglia (Nerve of Remak and pelvic plexuses). At embryonic day (E) 10, the two neural crest populations form overlapping subsets of neuronal and glia cell types. Surprisingly, the post-umbilical vagal neural crest much more closely resembles the sacral neural crest than the pre-umbilical vagal neural crest. However, some differences in cluster types were noted between vagal and sacral derived cells. Notably, RNA trajectory analysis suggests that the vagal neural crest maintains a neuronal/glial progenitor pool, whereas this cluster is depleted in the E10 sacral neural crest which instead has numerous enteric glia. The present findings reveal sacral neural crest contributions to the hindgut and associated peripheral ganglia and highlight the potential influence of the local environment and/or developmental timing in differentiation of neural crest-derived cells in the developing ENS.


Assuntos
Sistema Nervoso Entérico , Crista Neural , Trato Gastrointestinal , Neuroglia/metabolismo , Neurônios/fisiologia , Movimento Celular/fisiologia
2.
Dev Cell ; 57(18): 2181-2203.e9, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-36108627

RESUMO

Many developmental signaling pathways have been implicated in lineage-specific differentiation; however, mechanisms that explicitly control differentiation timing remain poorly defined in mammals. We report that murine Hedgehog signaling is a heterochronic pathway that determines the timing of progenitor differentiation. Hedgehog activity was necessary to prevent premature differentiation of second heart field (SHF) cardiac progenitors in mouse embryos, and the Hedgehog transcription factor GLI1 was sufficient to delay differentiation of cardiac progenitors in vitro. GLI1 directly activated a de novo progenitor-specific network in vitro, akin to that of SHF progenitors in vivo, which prevented the onset of the cardiac differentiation program. A Hedgehog signaling-dependent active-to-repressive GLI transition functioned as a differentiation timer, restricting the progenitor network to the SHF. GLI1 expression was associated with progenitor status across germ layers, and it delayed the differentiation of neural progenitors in vitro, suggesting a broad role for Hedgehog signaling as a heterochronic pathway.


Assuntos
Redes Reguladoras de Genes , Proteínas Hedgehog , Animais , Diferenciação Celular/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Proteína GLI1 em Dedos de Zinco/genética
3.
Proc Natl Acad Sci U S A ; 117(27): 15712-15723, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32561646

RESUMO

The mechanisms used by embryos to pattern tissues across their axes has fascinated developmental biologists since the founding of embryology. Here, using single-cell technology, we interrogate complex patterning defects and define a Hedgehog (Hh)-fibroblast growth factor (FGF) signaling axis required for anterior mesoderm lineage development during gastrulation. Single-cell transcriptome analysis of Hh-deficient mesoderm revealed selective deficits in anterior mesoderm populations, culminating in defects to anterior embryonic structures, including the pharyngeal arches, heart, and anterior somites. Transcriptional profiling of Hh-deficient mesoderm during gastrulation revealed disruptions to both transcriptional patterning of the mesoderm and FGF signaling for mesoderm migration. Mesoderm-specific Fgf4/Fgf8 double-mutants recapitulated anterior mesoderm defects and Hh-dependent GLI transcription factors modulated enhancers at FGF gene loci. Cellular migration defects during gastrulation induced by Hh pathway antagonism were mitigated by the addition of FGF4 protein. These findings implicate a multicomponent signaling hierarchy activated by Hh ligands from the embryonic node and executed by FGF signals in nascent mesoderm to control anterior mesoderm patterning.


Assuntos
Fator 4 de Crescimento de Fibroblastos/genética , Fator 8 de Crescimento de Fibroblasto/genética , Gastrulação/genética , Proteína GLI1 em Dedos de Zinco/genética , Animais , Padronização Corporal/genética , Linhagem da Célula/genética , Embrião de Galinha , Fatores de Crescimento de Fibroblastos/genética , Gástrula/crescimento & desenvolvimento , Gástrula/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas Hedgehog/genética , Mesoderma/crescimento & desenvolvimento , Mesoderma/metabolismo , Camundongos , Transdução de Sinais/genética , Análise de Célula Única , Transcriptoma/genética
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