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Forces shaping a Hox morphogenetic gene network

AuthorsSotillos, Sol ; Aguilar, Mario ; Castelli-Gair Hombría, James
Realizator gene
Homeotic gene
Issue Date2013
PublisherNational Academy of Sciences (U.S.)
CitationProceedings of the National Academy of Sciences of the USA 110(11): 4303-4308 (2013)
AbstractThe Abdominal-B selector protein induces organogenesis of the posterior spiracles by coordinating an organ-specific gene network. The complexity of this network begs the questions of how it originated and what selective pressures drove its formation. Given that the network likely formed in a piecemeal fashion, with elements recruited sequentially, we studied the consequences of expressing individual effectors of this network in naive epithelial cells.We found that, with exception of the Crossveinless-c (Cv-c) Rho GTPase-activating protein, most effectors exert little morphogenetic effect by themselves. In contrast, Cv-c expression causes cell motility and downregulates epithelial polarity and cell adhesion proteins. These effects differ in cells endogenously expressing Cv-c, which have acquired compensatory mechanisms. In spiracle cells, the down-regulation of polarity and E-cadherin expression caused by Cv-c-induced Rho1 inactivation are compensated for by the simultaneous spiracle up-regulation of guanine nucleotide exchange factor (GEF) proteins, cell polarity, and adhesion molecules. Other epithelial cells that have coopted Cv-c to their morphogenetic gene networks are also resistant to Cv-c's deleterious effects. We propose that cooption of a novel morphogenetic regulator to a selector cascade causes cellular instability, resulting in strong selective pressure that leads that same cascade to recruitmolecules that compensate it. This experimental-based hypothesis proposes how the frequently observed complex organogenetic gene networks are put together.
Publisher version (URL)http://dx.doi.org/10.1073/pnas.1212970110
Identifiersdoi: 10.1073/pnas.1212970110
e-issn: 1091-6490
Appears in Collections:(CABD) Artículos
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