Lee T, Hacohen N, Krasnow M, Montell D J
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205-2185, USA.
Genes Dev. 1996 Nov 15;10(22):2912-21. doi: 10.1101/gad.10.22.2912.
Receptor tyrosine kinases (RTKs) are members of a diverse class of signaling molecules well known for their roles in cell fate specification, cell differentiation, and oncogenic transformation. Recently several RTKs have been implicated in cell and axon motility, and RTKs are known to mediate chemotactic guidance of tissue culture cells. We have investigated whether the Drosophila FGF receptor homolog, Breathless (BTL), whose activity is necessary for each phase of branching morphogenesis in the embryonic tracheal system, might play a role in guiding the directed migration of tracheal cells. We found that expression of a constitutively active receptor during tracheal development interfered with directed tracheal cell migration and led to extra secondary and terminal branch-forming cells. Reduction in endogenous BTL signaling enhanced the cell migration defects while suppressing the ectopic branching defects. These results are consistent with a model for tracheal development in which spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates.
受体酪氨酸激酶（RTK）是一类多样的信号分子，因其在细胞命运决定、细胞分化和致癌转化中的作用而广为人知。最近，几种RTK与细胞和轴突运动有关，并且已知RTK介导组织培养细胞的趋化引导。我们研究了果蝇FGF受体同源物“呼吸急促”（BTL）是否可能在引导气管细胞的定向迁移中发挥作用，其活性对于胚胎气管系统分支形态发生的每个阶段都是必需的。我们发现，在气管发育过程中组成型活性受体的表达干扰了气管细胞的定向迁移，并导致额外的二级和终末分支形成细胞。内源性BTL信号的减少增强了细胞迁移缺陷，同时抑制了异位分支缺陷。这些结果与气管发育模型一致，在该模型中，空间调节的BTL活性引导气管细胞迁移，而定量调节的BTL活性决定二级和终末分支细胞命运的模式。
