Expression of HAND gene products may be sufficient for the differentiation of avian neural crest-derived cells into catecholaminergic neurons in culture
Expression of HAND gene products may be sufficient for the differentiation of avian neural crest-derived cells into catecholaminergic neurons in culture
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DOI：
10.1006/dbio.1999.9450
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发表时间：
1999-11-01
影响因子：
2.7
通讯作者：
Cserjesi, P
中科院分区：
文献类型：
--
作者：
Howard, M;Foster, DN;Cserjesi, P
DNA 结合蛋白基本螺旋-环-螺旋家族的成员在神经嵴衍生神经元亚群的发育中发挥重要作用。我们克隆了 dHAND (HAND2) 和 eHAND (HAND1) 的鸡同源物，这是基本的螺旋-环-螺旋 DNA 结合蛋白，其神经元表达仅限于交感神经和肠神经嵴衍生的神经节。编码 dHAND 和 eHAND 的转录本在汉堡和汉密尔顿阶段 17-18 开始在交感神经节中表达。体外对神经嵴衍生细胞中编码 HAND 基因的转录本进行反义阻断会导致神经发生显着减少。如果使用反义寡核苷酸阻断来减少编码 dHAND 和 eHAND 的转录物的表达，则儿茶酚胺能神经元的分化也会减少 52%。对神经嵴源性神经元的神经发生和表型表达的影响是特异的；阻断HAND基因表达对神经管源性神经元的体外分化没有明显影响。在补充有 2% 鸡胚提取物 (CEE) 的培养基中的非允许生长条件下，使用具有复制能力的禽逆转录病毒在体外神经嵴衍生细胞中组成型表达 HAND 基因，诱导早熟儿茶酚胺能分化。 HAND 基因产物的组成型表达导致在补充有 10% GEE 的培养基中生长的细胞的儿茶酚胺能分化显着增加，这是儿茶酚胺能发育的允许生长条件。这些结果表明，dHAND 和 eHAND 的神经嵴细胞的表达对于儿茶酚胺能表型表达可能是充分且必要的。 (C) 1999 年学术出版社。
Members of the basic helix-loop-helix family of DNA binding proteins have important roles in the development of subpopulations of neural crest-derived neurons. We have cloned the chicken homologues of dHAND (HAND2) and eHAND (HAND1), basic helix-loop-helix DNA binding proteins whose neuronal expression is restricted to sympathetic and enteric neural crest-derived ganglia. Transcripts encoding dHAND and eHAND are expressed in sympathetic ganglia beginning at Hamburger and Hamilton stage 17-18. Antisense blockade of transcripts encoding HAND genes in neural crest-derived cells in vitro results in a significant reduction in neurogenesis. Differentiation of catecholaminergic neurons is also reduced by 52% if the expression of transcripts encoding dHAND and eHAND is reduced using antisense oligonucleotide blockade. The effect on neurogenesis and phenotypic expression of neural crest-derived neurons is specific; blockade of HAND gene expression has no apparent influence on the differentiation in vitro of neural tube-derived neurons. Use of a replication-competent avian retrovirus to constitutively express HAND genes in neural crest-derived cells in vitro, under nonpermissive growth conditions in medium supplemented with 2% chick embryo extract (CEE), induced precocious catecholaminergic differentiation. Constitutive expression of HAND gene products resulted in a significant increase in catecholaminergic differentiation of cells grown in medium supplemented with 10% GEE, a permissive growth condition for catecholaminergic development. These results suggest that the expression by neural crest cells of dHAND and eHAND may be both sufficient and necessary for catecholaminergic phenotypic expression. (C) 1999 Academic Press.