Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Abstract

The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results. Developmental Dynamics 235:2337-2352, 2006.

The developing female genital tract: from genetics to epigenetics

“…Another well-studied signalling molecule in the context of embryonic development is retinoic acid (RA), a morphogen derived from vitamin A. RA seems to be particularly involved in antero-posterior patterning both along the body axis and in developing limb bud (Dreyer and Ellinger-Ziegelbauer 1996;Robert and Lallemand 2006). Compound null mutations of its cognate receptors (RARs and RXRs) lead to a broad range of developmental abnormalities, among which severe defects of the urogenital system (Mendelsohn et al 1994).…”

“…Incidentally, a mutation in the Wnt4 gene was discovered in a 46, XX woman presenting a somewhat similar phenotype: complete absence of MD-derived structures and clinical signs of androgens excess (Biason-Lauber et al 2004). Interestingly, Wnt4 and Fgf9 seem to constitute mutual antagonistic signals in the bipotential gonad, regulating gonadal differentiation into female or male pathway by imbalance between them ( Kim et al 2006).Another well-studied signalling molecule in the context of embryonic development is retinoic acid (RA), a morphogen derived from vitamin A. RA seems to be particularly involved in antero-posterior patterning both along the body axis and in developing limb bud (Dreyer and Ellinger-Ziegelbauer 1996;Robert and Lallemand 2006). Compound null mutations of its cognate receptors (RARs and RXRs) lead to a broad range of developmental abnormalities, among which severe defects of the urogenital system (Mendelsohn et al 1994).…”

Canine Polydactyl Mutations With Heterogeneous Origin in the Conserved Intronic Sequence of LMBR1

“…The DC-2 mutation was identified in 26 affected individuals of Western breeds with either heterozygosity (G/A in 14) or homozygosity (A/A in 12), whereas the 23 unaffected individuals were homozygous (G/G). On the other hand, there were seven more MCS in the candidate region, three in the intergenic regions between the NOM1 and LMBR1 genes, and four in the intronic regions (Sharpe et al 1999;Lettice et al 2003;Robert and Lallemand 2006) in LMBR1 ( Figure 1A and supplemental Figure S2). A comparison of the sequences in this region did not disclose any differences between normal and PPD animals (data not shown).…”

“…The embryonic period of dogs is defined as 13-34 days after fertilization, in which the limb buds are visible at 24-26 days of embryo development (Ruvinsky 2001). This period corresponds to 10-12 embryonic days for mice, during which the Shh expression in the ZPA of a limb bud is apparent (Robert and Lallemand 2006). We obtained 13 dog embryos of days 23-26 from four Sapsarees in a natural estrus cycle, which were generated after crossing heterozygous Sapsarees with PPD.…”

Genetic aspects of vagina and the uterus aplasia: the history

“…На эту тему прове-ден ряд исследований по изучению влияния эндо-кринных «прерывателей» -диэтилстильбэстрола (DES -синтетический эстроген) [22], ретиноевой кислоты [23], галактозы [24], фолатного статуса [25], однако не было доказано влияние таких воздействий как непосредственной причины при формировании аплазии матки и влагалища. В ракурсе последних до-стижений медицины, связанных с рождением ребен-ка у женщины с синдромом МРКХ и трансплантиро-ванной маткой, большое внимание уделяется потен-циальному побочному действию иммуносупрессив-ной терапии, необходимой в таких случаях.…”