Huber Katrin, Karch Nicole, Ernsberger Uwe, Goridis Christo, Unsicker Klaus
Neuroanatomy, Interdisciplinary Center for Neurosciences, University of Heidelberg, INF 307, D-69120 Heidelberg, Germany.
Dev Biol. 2005 Mar 15;279(2):501-8. doi: 10.1016/j.ydbio.2005.01.007.
Phox2B, a homeodomain transcription factor closely related to Phox2A, is expressed in peripheral and central noradrenergic neurons. In neural crest (NC) derivatives Phox2B is restricted to sympathetic and parasympathetic ganglia, enteric neurons, and adrenal and extraadrenal chromaffin cells. Similar to MASH-1, Phox2B has been implicated in synchronizing pan-neuronal and catecholaminergic phenotype-specific aspects of neurogenesis. The role of Phox2B for the differentiation of the neuroendocrine NC derivatives, the adrenal medullary chromaffin cells, has not been explored. We have previously reported that in MASH-1-deficient mice most chromaffin cells are arrested at the early neuroblast stage and lack catecholaminergic differentiation. We show now that in Phox2B knockout/lacZ knockin mice the maturation of presumptive chromaffin cells is arrested at an even earlier stage of development. The cells lack the catecholaminergic marker enzyme TH and fail to form a centrally located medulla. In contrast to MASH-1 (-/-) mice they do not express dHand, Phox2A, c-ret, neurofilament, neuron-specific tubulin, and NCAM and appear ultrastructurally more immature. Many of these cells die by apoptosis. Despite the complete lack of differentiation, few lacZ-positive adrenal cells can still be found at E16.5. We conclude that Phox2B regulates very early events in the differentiation of adrenal chromaffin cells distinct to steps, which essentially require MASH-1.
Phox2B是一种与Phox2A密切相关的同源域转录因子，在外周和中枢去甲肾上腺素能神经元中表达。在神经嵴（NC）衍生物中，Phox2B局限于交感和副交感神经节、肠神经元以及肾上腺和肾上腺外嗜铬细胞。与MASH-1相似，Phox2B参与了神经发生过程中泛神经元和儿茶酚胺能表型特异性方面的同步。Phox2B在神经内分泌NC衍生物即肾上腺髓质嗜铬细胞分化中的作用尚未得到研究。我们之前报道过，在MASH-1缺陷小鼠中，大多数嗜铬细胞停滞在早期神经母细胞阶段，缺乏儿茶酚胺能分化。我们现在表明，在Phox2B基因敲除/ lacZ基因敲入小鼠中，假定嗜铬细胞的成熟在发育的更早阶段就被阻断。这些细胞缺乏儿茶酚胺能标记酶TH，无法形成位于中央的髓质。与MASH-1（-/-）小鼠不同，它们不表达dHand、Phox2A、c-ret、神经丝、神经元特异性微管蛋白和NCAM，并且在超微结构上显得更不成熟。许多这些细胞通过凋亡死亡。尽管完全缺乏分化，但在E16.5时仍能发现少数lacZ阳性的肾上腺细胞。我们得出结论，Phox2B调节肾上腺嗜铬细胞分化中非常早期的事件，这些事件与基本上需要MASH-1的步骤不同。
