Retinoic Acid Signaling induces Ets Repressor proteins to promote primary neurogenesis

发育中的神经组织细胞在增殖（细胞生长/分裂）和分化（细胞分化为成熟神经元）之间表现出一种微妙的平衡。维甲酸是维生素A衍生的一种重要分子，在抑制细胞增殖和促进细胞分化中起着重要作用。维甲酸如何控制这一过程以促进成熟神经元的发育尚不清楚。布隆伯格实验室发现了一种名为ETS2抑制因子（Erf）的基因，它在神经发育中起着关键作用。Erf的表达受视黄酸控制，视黄酸或Erf的缺失会抑制神经元的形成。为了测试Erf如何在视黄酸下游发挥作用，Blumberg实验室将使用分子方法来抑制或增加早期胚胎中Erf的功能，并研究参与神经前体增殖和神经元分化的重要基因的表达。他们希望确定维甲酸Erf及其靶基因控制神经组织中增殖和分化之间转换的分子途径。揭示这一遗传程序及其功能所需的分子相互作用将提供有关增殖-分化开关的重要和广泛适用的细节。这将大大增加对发育如何工作的理解，特别是干细胞如何决定停止分裂并分化成各种成熟细胞类型。这项研究的更广泛影响在于教育和培训下一代科学家（包括妇女和代表性不足的群体），以及广泛传播联邦政府资助的科学成果。此外，这些研究将通过推动生物学中一个基本重要但鲜为人知的过程的知识前沿，从而使整个社会受益。

Cells in developing neural tissue demonstrate an exquisite balance between proliferation (cell growth/division) and differentiation (the specialization of cells into mature neurons). Retinoic acid, an important molecule derived from Vitamin A, is a critical participant in inhibiting cell proliferation and encouraging differentiation. How retinoic acid controls this process to promote the development of mature neurons is not well understood. The Blumberg laboratory identified a gene named ETS2 Repressor Factor (Erf) that plays a key role in neural development. Erf expression is controlled by retinoic acid and loss of retinoic acid or Erf inhibits the formation of neurons. To test how Erf functions downstream of retinoic acid, the Blumberg laboratory will use a molecular approach to inhibit or increase the function of Erf in early embryos and study the expression of important genes involved in the proliferation of neural precursors and in the differentiation of neurons. They expect to identify the molecular pathway through which retinoic acid, Erf and its target genes control the switch between proliferation and differentiation in neural tissue. Unraveling this genetic program and the molecular interactions required for it to function will provide important and broadly applicable details about the proliferation-differentiation switch. This will greatly increase the understanding of how development works and, in particular, how stem cells decide to stop dividing and differentiate into various mature cell types. The broader impacts of this research are in educating and training the next generation of scientists (including women and underrepresented groups) and in disseminating the results of Federally funded science broadly. Furthermore, these studies will benefit society in general by pushing back the frontiers of knowledge regarding a fundamentally important but poorly understood process in Biology.