Shh signaling influences the phenotype of Pitx1-/- hindlimbs.

Forelimbs (FLs) and hindlimbs (HLs) develop under the instructive and integrated guidance of signaling centers and transcription factor (TF) action. The development of structures specific to each limb type depends on the limb-specific modulation of these integrated components. Pitx1 is a transcription factor gene expressed in HL, absent in FL, and required for HL-specific patterning and development, in particular for formation of anterior HL skeletal elements.

Regulatory integration of Hox factor activity with T-box factors in limb development.

In tetrapods, , and Hox cluster genes are crucial for forelimb and hindlimb development and mutations in these genes are responsible for congenital limb defects. The molecular basis of their integrated mechanisms of action in the context of limb development remains poorly understood. We studied Tbx4 and Hoxc10 owing to their overlapping loss-of-function phenotypes and colocalized expression in mouse hindlimb buds.

directly modulates the core limb development program to implement hindlimb identity.

Forelimbs (FLs) and hindlimbs (HLs) develop complex musculoskeletal structures that rely on the deployment of a conserved developmental program. , a transcription factor gene with expression restricted to HL and absent from FL, plays an important role in generating HL features. The genomic mechanisms by which effects HL identity remain poorly understood.

Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13.

The combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in Hoxa13; Hoxd13 limbs.

Decoupling the function of Hox and Shh in developing limb reveals multiple inputs of Hox genes on limb growth.

Limb development relies on an exquisite coordination between growth and patterning, but the underlying mechanisms remain elusive. Anterior-posterior and proximal-distal specification initiates in early limb bud concomitantly with the proliferative expansion of limb cells. Previous studies have shown that limb bud growth initially relies on fibroblast growth factors (FGFs) produced in the apical ectodermal ridge (AER-FGFs), the maintenance of which relies on a positive-feedback loop involving sonic hedgehog (Shh) and the BMP antagonist gremlin 1 (Grem1).

Visceroptosis of the bowel in the hypermobility type of Ehlers-Danlos syndrome: presentation of a rare manifestation and review of the literature.

Gastrointestinal complications are common in patients with Ehlers-Danlos syndrome, affecting up to 50% of individuals depending on the subtype. The spectrum of gastrointestinal manifestations is broad and ranges from life threatening spontaneous perforation of the visceral organs to a more benign functional symptoms. Here we describe the clinical and radiographic manifestations of visceroptosis of the bowel, a rare complication of Ehlers-Danlos syndrome that is characterized by prolapse of abdominal organs below their natural position.