Journal of Developmental Biology最新文献

RNA binding proteins (RBPs) play a fundamental role in the post-transcriptional regulation of gene expression within the germline and nervous system. This is underscored by the prevalence of mutations within RBP-encoding genes being implicated in infertility and neurological disease. We previously described roles for the highly conserved RBP Caper in neurite morphogenesis in the Drosophila larval peripheral system and in locomotor behavior. However, caper function has not been investigated outside the nervous system, although it is widely expressed in many different tissue types during embryogenesis. Here, we describe novel roles for Caper in fertility and mating behavior. We find that Caper is expressed in ovarian follicles throughout oogenesis but is dispensable for proper patterning of the egg chamber. Additionally, reduced caper function, through either a genetic lesion or RNA interference-mediated knockdown of caper in the female germline, results in females laying significantly fewer eggs than their control counterparts. Moreover, this phenotype is exacerbated with age. caper dysfunction also results in partial embryonic and larval lethality. Given that caper is highly conserved across metazoa, these findings may also be relevant to vertebrates.

Cilia are microtubule-based organelles that project from the cell surface. In humans and other vertebrates, possession of a single cilium structure enables an assortment of cellular processes ranging from mechanosensation to fluid propulsion and locomotion. Interestingly, cells can possess a single cilium or many more, where so-called multiciliated cells (MCCs) possess apical membrane complexes with several dozen or even hundreds of motile cilia that beat in a coordinated fashion. Development of MCCs is, therefore, integral to control fluid flow and/or cellular movement in various physiological processes. As such, MCC dysfunction is associated with numerous pathological states. Understanding MCC ontogeny can be used to address congenital birth defects as well as acquired disease conditions. Today, researchers used both in vitro and in vivo experimental models to address our knowledge gaps about MCC specification and differentiation. In this review, we summarize recent discoveries from our lab and others that have illuminated new insights regarding the genetic pathways that direct MCC ontogeny in the embryonic kidney using the power of the zebrafish animal model.

Primary cilia are specialized, microtubule-based structures projecting from the surface of most mammalian cells. These organelles are thought to primarily act as signaling hubs and sensors, receiving and integrating extracellular cues. Several important signaling pathways are regulated through the primary cilium including Sonic Hedgehog (Shh) and Wnt signaling. Therefore, it is no surprise that mutated genes encoding defective proteins that affect primary cilia function or structure are responsible for a group of disorders collectively termed ciliopathies. The severe neurologic abnormalities observed in several ciliopathies have prompted examination of primary cilia structure and function in other brain disorders. Recently, neuronal primary cilia defects were observed in monogenic neurodevelopmental disorders that were not traditionally considered ciliopathies. The molecular mechanisms of how these genetic mutations cause primary cilia defects and how these defects contribute to the neurologic manifestations of these disorders remain poorly understood. In this review we will discuss monogenic neurodevelopmental disorders that exhibit cilia deficits and summarize findings from studies exploring the role of primary cilia in the brain to shed light into how these deficits could contribute to neurologic abnormalities.

Pelvic girdles, fins and claspers are evolutionary novelties first recorded in jawed vertebrates. Over the course of the evolution of chondrichthyans (cartilaginous fish) two trends in the morphology of the pelvic skeleton have been suggested to have occurred. These evolutionary shifts involved both an enlargement of the metapterygium (basipterygium) and a transition of fin radial articulation from the pelvic girdle to the metapterygium. To determine how these changes in morphology have occurred it is essential to understand the development of extant taxa as this can indicate potential developmental mechanisms that may have been responsible for these changes. The study of the morphology of the appendicular skeleton across development in chondrichthyans is almost entirely restricted to the historical literature with little contemporary research. Here, we have examined the morphology and development of the pelvic skeleton of a holocephalan chondrichthyan, the elephant shark (Callorhinchus milii), through a combination of dissections, histology, and nanoCT imaging and redescribed the pelvic skeleton of Cladoselache kepleri (NHMUK PV P 9269), a stem holocephalan. To put our findings in their evolutionary context we compare them with the fossil record of chondrichthyans and the literature on pelvic development in elasmobranchs from the late 19th century. Our findings demonstrate that the pelvic skeleton of C. milii initially forms as a single mesenchymal condensation, consisting of the pelvic girdle and a series of fin rays, which fuse to form the basipterygium. The girdle and fin skeleton subsequently segment into distinct components whilst chondrifying. This confirms descriptions of the early pelvic development in Scyliorhinid sharks from the historical literature and suggests that chimaeras and elasmobranchs share common developmental patterns in their pelvic anatomy. Alterations in the location and degree of radial fusion during early development may be the mechanism responsible for changes in pelvic fin morphology over the course of the evolution of both elasmobranchs and holocephalans, which appears to be an example of parallel evolution.

The development of multicellular organisms requires a tightly coordinated network of cellular processes and intercellular signalling. For more than 20 years, it has been known that primary cilia are deeply involved in the mediation of intercellular signalling and that ciliary dysfunction results in severe developmental defects. Cilia-mediated signalling regulates cellular processes such as proliferation, differentiation, migration, etc. Another cellular process ensuring proper embryonic development is cell death. While the effect of cilia-mediated signalling on many cellular processes has been extensively studied, the relationship between primary cilia and cell death remains largely unknown. This article provides a short review on the current knowledge about this relationship.

Primary cilia are microtube-based organelles that extend from the cell surface and function as biochemical and mechanical extracellular signal sensors. Primary cilia coordinate a series of signaling pathways during development. Cilia dysfunction leads to a pleiotropic group of developmental disorders, termed ciliopathy. Phosphoinositides (PIs), a group of signaling phospholipids, play a crucial role in development and tissue homeostasis by regulating membrane trafficking, cytoskeleton reorganization, and organelle identity. Accumulating evidence implicates the involvement of PI species in ciliary defects and ciliopathies. The abundance and localization of PIs in the cell are tightly regulated by the opposing actions of kinases and phosphatases, some of which are recently discovered in the context of primary cilia. Here, we review several cilium-associated PI kinases and phosphatases, including their localization along cilia, function in regulating the ciliary biology under normal conditions, as well as the connection of their disease-associated mutations with ciliopathies.

Neuronal subtypes in the mammalian cerebral cortex are determined by both intrinsic and extrinsic mechanisms during development. However, the extrinsic cues that are involved in this process remain largely unknown. Here, we investigated the role of sonic hedgehog (Shh) in glutamatergic cortical subtype specification. We found that E14.5-born, but not E15.5-born, neurons with elevated Shh expression frequently differentiated into layer 4 subtypes as judged by the cell positioning and molecular identity. We further found that this effect was achieved indirectly through the regulation of cell positioning rather than the direct activation of layer 4 differentiation programs. Together, we provided evidence that Shh, an extrinsic factor, plays an important role in the specification of cortical superficial layer subtypes.

Organophosphate (OP) insecticides are used to eliminate agricultural threats posed by insects, through inhibition of the neurotransmitter acetylcholinesterase (AChE). These potent neurotoxins are extremely efficacious in insect elimination, and as such, are the preferred agricultural insecticides worldwide. Despite their efficacy, however, estimates indicate that only 0.1% of organophosphates reach their desired target. Moreover, multiple studies have shown that OP exposure in both humans and animals can lead to aberrations in embryonic development, defects in childhood neurocognition, and substantial contribution to neurodegenerative diseases such as Alzheimer's and Motor Neurone Disease. Here, we review the current state of knowledge pertaining to organophosphate exposure on both embryonic development and/or subsequent neurological consequences on behaviour, paying particular attention to data gleaned using an excellent animal model, the zebrafish (Danio rerio).

The Hox gene cluster, responsible for patterning of the head-tail axis, is an ancestral feature of all bilaterally symmetrical animals (the Bilateria) that remains intact in a wide range of species. We can say that the Hox cluster evolved successfully only once since it is commonly the same in all groups, with labial-like genes at one end of the cluster expressed in the anterior embryo, and Abd-B-like genes at the other end of the cluster expressed posteriorly. This review attempts to make sense of the Hox gene cluster and to address the following questions. How did the Hox cluster form in the protostome-deuterostome last common ancestor, and why was this with a particular head-tail polarity? Why is gene clustering usually maintained? Why is there collinearity between the order of genes along the cluster and the positions of their expressions along the embryo? Why do the Hox gene expression domains overlap along the embryo? Why have vertebrates duplicated the Hox cluster? Why do Hox gene knockouts typically result in anterior homeotic transformations? How do animals adapt their Hox clusters to evolve new structural patterns along the head-tail axis?

Multiple motile cilia are formed at the apical surface of multi-ciliated cells in the epithelium of the oviduct or the fallopian tube, the trachea, and the ventricle of the brain. Those cilia beat unidirectionally along the tissue axis, and this provides a driving force for directed movements of ovulated oocytes, mucus, and cerebrospinal fluid in each of these organs. Furthermore, cilia movements show temporal coordination between neighboring cilia. To establish such coordination of cilia movements, cilia need to sense and respond to various cues, including the organ's orientation and movements of neighboring cilia. In this review, we discuss the mechanisms by which cilia movements of multi-ciliated cells are coordinated, focusing on planar cell polarity and the cytoskeleton, and highlight open questions for future research.