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Pitx2 regulates gonad morphogenesis.

ABSTRACT: Organ shape and size, and, ultimately, organ function, relate in part to the cell and tissue spatial arrangement that takes place during embryonic development. Despite great advances in the genetic regulatory networks responsible for tissue and organ development, it is not yet clearly understood how specific gene functions are linked to the specific morphogenetic processes underlying the internal organ asymmetries found in vertebrate animals. During female chick embryogenesis, and in contrast to males where both testes develop symmetrically, asymmetrical gonad morphogenesis results in only one functional ovary. The disposition of paired organs along the left-right body axis has been shown to be regulated by the activity of the homeobox containing gene pitx2. We have found that pitx2 regulates cell adhesion, affinity, and cell recognition events in the developing gonad primordium epithelia. This in turn not only allows for proper somatic development of the gonad cortex but also permits the proliferation and differentiation of primordial germ cells. We illustrate how Pitx2 activity directs asymmetrical gonad morphogenesis by controlling mitotic spindle orientation of the developing gonad cortex and how, by modulating cyclinD1 expression during asymmetric ovarian development, Pitx2 appears to control gonad organ size. All together our observations indicate that the effects elicited by Pitx2 during the development of the female chick ovary are critical for cell topology, growth, fate, and ultimately organ morphogenesis and function.

SUBMITTER: Rodriguez-Leon J

PROVIDER: S-EPMC2516275 | biostudies-other | 2008 Aug

REPOSITORIES: biostudies-other

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Pitx2 regulates gonad morphogenesis.

Rodríguez-León Joaquín J Rodríguez Esteban Concepción C Martí Mercè M Santiago-Josefat Belén B Dubova Ilir I Rubiralta Xavier X Izpisúa Belmonte Juan Carlos JC

Proceedings of the National Academy of Sciences of the United States of America 20080804 32

Organ shape and size, and, ultimately, organ function, relate in part to the cell and tissue spatial arrangement that takes place during embryonic development. Despite great advances in the genetic regulatory networks responsible for tissue and organ development, it is not yet clearly understood how specific gene functions are linked to the specific morphogenetic processes underlying the internal organ asymmetries found in vertebrate animals. During female chick embryogenesis, and in contrast to ...[more]

PMID: 18678914

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Project description:Mechanical stability is a fundamental and essential property of epithelial cell sheets. It is in large part determined by cell-cell adhesion sites that are tightly integrated by the cortical cytoskeleton. An intimate crosstalk between the adherens junction-associated contractile actomyosin system and the desmosome-anchored keratin intermediate filament system is decisive for dynamic regulation of epithelial mechanics. A major question in the field is whether and in which way mechanical stress affects junctional plasticity. This is especially true for the desmosome-keratin scaffold whose role in force-sensing is virtually unknown. To examine this question, we inactivated the actomyosin system in human keratinocytes (HaCaT) and canine kidney cells (MDCK) and monitored changes in desmosomal protein turnover. Partial inhibition of myosin II by para-nitro-blebbistatin led to a decrease of the cells' elastic modulus and to reduced desmosomal protein turnover in regions where nascent desmosomes are formed and, to a lower degree, in regions where larger, more mature desmosomes are present. Interestingly, desmosomal proteins are affected differently: a significant decrease in turnover was observed for the desmosomal plaque protein desmoplakin I (DspI), which links keratin filaments to the desmosomal core, and the transmembrane cadherin desmoglein 2 (Dsg2). On the other hand, the turnover of another type of desmosomal cadherin, desmocollin 2 (Dsc2), was not significantly altered under the tested conditions. Similarly, the turnover of the adherens junction-associated E-cadherin was not affected by the low doses of para-nitro-blebbistatin. Inhibition of actin polymerization by low dose latrunculin B treatment and of ROCK-driven actomyosin contractility by Y-27632 treatment also induced a significant decrease in desmosomal DspI turnover. Taken together, we conclude that changes in the cortical force balance affect desmosome formation and growth. Furthermore, they differentially modulate desmosomal protein turnover resulting in changes of desmosome composition. We take the observations as evidence for a hitherto unknown desmosomal mechanosensing and mechanoresponse pathway responding to an altered force balance.

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Pitx2 regulates gonad morphogenesis.

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Pitx2 regulates gonad morphogenesis.

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