RESUMO
NF-protocadherin (NFPC)-mediated cell-cell adhesion plays a critical role in vertebrate neural tube formation. NFPC is also expressed during the period of axon tract formation, but little is known about its function in axonogenesis. Here we have tested the role of NFPC and its cytosolic cofactor template-activating factor 1 (TAF1) in the emergence of the Xenopus retinotectal projection. NFPC is expressed in the developing retina and optic pathway and is abundant in growing retinal axons. Inhibition of NFPC function in developing retinal ganglion cells (RGCs) severely reduces axon initiation and elongation and suppresses dendrite genesis. Furthermore, an identical phenotype occurs when TAF1 function is blocked. These data provide evidence that NFPC regulates axon initiation and elongation and indicate a conserved role for TAF1, a transcriptional regulator, as a downstream cytosolic effector of NFPC in RGCs.
Assuntos
Axônios/fisiologia , Caderinas/fisiologia , Proteínas de Ligação a DNA/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Células Ganglionares da Retina/citologia , Proteínas de Xenopus/fisiologia , Animais , Embrião não Mamífero , Proteínas de Fluorescência Verde/metabolismo , Mutação/genética , Técnicas de Cultura de Órgãos , Protocaderinas , Retina/citologia , Transfecção/métodos , XenopusRESUMO
Protocadherins are members of the cadherin superfamily of cell adhesion molecules proposed to play important roles in early development, but whose mechanisms of action are largely unknown. We examined the function of NF-protocadherin (NFPC), a novel cell adhesion molecule essential for the histogenesis of the embryonic ectoderm in Xenopus, and demonstrate that the cellular protein TAF1, previously identified as a histone-associated protein, binds the NFPC cytoplasmic domain. NFPC and TAF1 coprecipitate from embryo extracts when ectopically expressed, and TAF1 can rescue the ectodermal disruptions caused by a dominant-negative NFPC construct lacking the extracellular domain. Furthermore, disruptions in either NFPC or TAF1 expression, using NFPC- or TAF1-specific antisense morpholinos, result in essentially identical ectodermal defects. These results indicate a role for TAF1 in the differentiation of the embryonic ectoderm, as a cytosolic cofactor of NFPC.