Insights into digit evolution from a fate map study of the forearm using Chameleon, a new transgenic chicken line.

The cellular and genetic networks that contribute to the development of the zeugopod (radius and ulna of the forearm, tibia and fibula of the leg) are not well understood, although these bones are susceptible to loss in congenital human syndromes and to the action of teratogens such as thalidomide. Using a new fate-mapping approach with the Chameleon transgenic chicken line, we show that there is a small contribution of SHH-expressing cells to the posterior ulna, posterior carpals and digit 3. We establish that although the majority of the ulna develops in response to paracrine SHH signalling in both the chicken and mouse, there are differences in the contribution of SHH-expressing cells between mouse and chicken as well as between the chicken ulna and fibula.

The Transcriptome of Chicken Migratory Primordial Germ Cells Reveals Intrinsic Sex Differences and Expression of Hallmark Germ Cell Genes.

Primordial germ cells (PGCs) are germline-restricted embryonic cells that form the functional gametes of the adult animal. The use of avian PGCs in biobanking and producing genetically modified birds has driven research on the in vitro propagation and manipulation of these embryonic cells. In avian species, PGCs are hypothesized to be sexually undetermined at an early embryonic stage and undergo differentiation into an oocyte or spermatogonial fate dictated by extrinsic factors present in the gonad.

The transcriptional signature associated with human motile cilia.

Cilia are complex microtubule-based organelles essential to a range of processes associated with embryogenesis and tissue homeostasis. Mutations in components of these organelles or those involved in their assembly may result in a diverse set of diseases collectively known as ciliopathies. Accordingly, many cilia-associated proteins have been described, while those distinguishing cilia subtypes are poorly defined.

An analysis of anterior segment development in the chicken eye.

Precise anterior segment (AS) development in the vertebrate eye is essential for maintaining ocular health throughout life. Disruptions to genetic programs can lead to severe structural AS disorders at birth, while more subtle AS defects may disrupt the drainage of ocular fluids and cause dysregulation of intraocular pressure homeostasis, leading to progressive vision loss. To date, the mouse has served as the major model to study AS development and pathogenesis.

Canine Brachycephaly Is Associated with a Retrotransposon-Mediated Missplicing of SMOC2.

In morphological terms, "form" is used to describe an object's shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form.

A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma.

Ocular coloboma (OC) is a defect in optic fissure closure and is a common cause of severe congenital visual impairment. Bilateral OC is primarily genetically determined and shows marked locus heterogeneity. Whole-exome sequencing (WES) was used to analyze 12 trios (child affected with OC and both unaffected parents).

TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23).

Joubert syndrome (JBTS) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems. Mutations in known JBTS genes account for approximately half of the cases. By homozygosity mapping and whole-exome sequencing, we identified a novel locus, JBTS23, with a homozygous splice site mutation in KIAA0586 (alias TALPID3), a known lethal ciliopathy locus in model organisms.

Loss of cilia causes embryonic lung hypoplasia, liver fibrosis, and cholestasis in the talpid3 ciliopathy mutant.

Sonic hedgehog plays an essential role in maintaining hepatoblasts in a proliferative non-differentiating state during embryogenesis. Transduction of the Hedgehog signaling pathway is dependent on the presence of functional primary cilia and hepatoblasts, therefore, must require primary cilia for normal function. In congenital syndromes in which cilia are absent or non-functional (ciliopathies) hepatorenal fibrocystic disease is common and primarily characterized by ductal plate malformations which underlie the formation of liver cysts, as well as less commonly, by hepatic fibrosis, although a role for abnormal Hedgehog signal transduction has not been implicated in these phenotypes.

The chicken left right organizer has nonmotile cilia which are lost in a stage-dependent manner in the talpid(3) ciliopathy.

Motile cilia are an essential component of the mouse, zebrafish, and Xenopus laevis Left Right Organizers, generating nodal flow and allowing the reception and transduction of mechanosensory signals. Nonmotile primary cilia are also an important component of the Left Right Organizer's chemosensory mechanism. It has been proposed in the chicken that signaling in Hensen's node, the Left Right Organizer of the chicken, is independent of cilia, based on a lack of evidence of motile cilia or nodal flow.

Failure of centrosome migration causes a loss of motile cilia in talpid(3) mutants.

Background: Loss of function mutations in the centrosomal protein TALPID3 (KIAA0586) cause a failure of primary cilia formation in animal models and are associated with defective Hedgehog signalling. It is unclear, however, if TALPID3 is required only for primary cilia formation or if it is essential for all ciliogenesis, including that of motile cilia in multiciliate cells.

Results: FOXJ1, a key regulator of multiciliate cell fate, is expressed in the dorsal neuroectoderm of the chicken forebrain and hindbrain at stage 20HH, in areas that will give rise to choroid plexuses in both wt and talpid(3) embryos.

Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick.

PHOSPHO1 is a bone-specific phosphatase implicated in the initiation of inorganic phosphate generation for matrix mineralization. The control of mineralization is attributed to the actions of tissue-nonspecific alkaline phosphatase (TNAP). However, matrix vesicles (MVs) containing apatite crystals are present in patients with hypophosphatasia as well as TNAP null (Akp2(-/-)) mice.