Mutations in the ligand-binding domain of the thyroid hormone receptor β (TRβ) lead to resistance to thyroid hormone (RTH). These TRβ mutants function in a dominant-negative fashion to interfere with the transcription activity of wild-type thyroid hormone receptors (TRs), leading to dysregulation of the pituitary-thyroid axis and resistance in peripheral tissues. The molecular mechanism by whic...

During heart formation, the grows and undergoes dramatic morphogenesis to achieve efficient embryonic function. Both in fish amniotes, much of growth occurring after initial tube formation arises from second field (SHF)-derived progenitor cell addition arterial pole, allowing chamber formation. In zebrafish, this process has been extensively studied during life, but it is unclear how larval car...

Background: Parkinson’s disease is a neurodegenerative caused by the loss of dopaminergic neurons in substantia nigra pars compacta. Among first identified causes autosomal recessive were mutations parkin gene. Independently, we and other groups have developed various knockout mice, none displayed degeneration nigra. Interestingly, has been reported line (exon 3 deletion) carrying an additional...

Mutations of orphan nuclear receptors SF1 and DAX1 each cause adrenal insufficiency and gonadal dysgenesis in humans, although the pathological features are distinct. Because Dax1 antagonizes Sf1-mediated transcription in vitro, we hypothesized that Dax1 deficiency would compensate for allelic loss of Sf1. In studies of the developing testis, expression of the fetal Leydig cell markers Cyp17 an...

The formation of the anterior and intermediate lobes of the pituitary gland is a multi-step process regulated by cell-cell interactions involving a number of signaling pathways and by cascades of cell-intrinsic transcription factors. The LIM-homeodoamin protein Lhx3 has previously been shown to play an essential role in the growth of Rathke's pouch, a primordium of the anterior and intermediate...

Leishmania parasites possess a unique and complex cytoskeletal structure termed flagellum attachment zone (FAZ) connecting the base of to one side flagellar pocket (FP), an invagination cell body membrane sole site for endocytosis exocytosis. This is involved in FP architecture morphogenesis, but its precise role molecular composition remain enigmatic. Here, we characterized FAZ7, only known FA...

Von Willebrand disease (VWD)-type 2B originates from a gain-of-function mutation in von Willebrand factor (VWF), resulting in enhanced platelet binding. Clinical manifestations include increased bleeding tendency, loss of large multimers, thrombocytopenia, and circulating platelet aggregates. We developed a mouse model to study phenotypic consequences of VWD-type 2B mutations in murine VWF: mVW...

Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cil...

Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cil...

Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cil...