On the trail of the 'new head' in Les Treilles

The vertebrate brain develops in association with neighboring tissues: neural crest, placodes, mesoderm and endoderm. The molecular and evolutionary relationships between the forming nervous system and the other craniofacial structures were at the focus of a recent meeting at the Fondation des Treilles in France. Entitled 'Relationships between Craniofacial and Neural Development', the meeting brought together researchers working on diverse species, the findings of whom provide clues as to the origin and diversity of the brain and facial regions that are involved in forming the 'new head' of vertebrates

Competence, specification and commitment to an olfactory placode fate

The nasal placode shares a common origin with other sensory placodes within a pre-placodal domain at the cranial neural plate border. However, little is known about early events in nasal placode development as it segregates from prospective lens, neural tube and epidermis. Here, Dlx3, Dlx5, Pax6 and the pan-neuronal marker Hu serve as molecular labels to follow the maturation of olfactory precursors over time. When competence to form olfactory placode was tested by grafting ectoderm from different axial levels to the anterior neural fold, we found that competence is initially broad for head, but not trunk, ectoderm and declines rapidly with time. Isolated olfactory precursors are specified by HH10, concomitant with their complete segregation from other placodal, epidermal and neural progenitors. Heterotopic transplantation of olfactory progenitors reveals they are capable of autonomous differentiation only 12 hours later, shortly before overt placode invagination at HH14. Taken together, these results show that olfactory placode development is a step-wise process whereby signals from adjacent tissues specify competent ectoderm at or before HH10, followed by gradual commitment just prior to morphological differentiation

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: mirror of the past ?

Summary: In modern vertebrates upper and lower jaws are morphologically different. Both develop from the mandibular arch, which is colonized mostly by Hox-free neural crest cells. Here we show that simultaneous inactivation of the murine homeobox genes Dlx5 and Dlx6 results in the transformation of the lower jaw into an upper jaw and in symmetry of the snout. This is the first homeotic-like transformation found in this Hox-free region after gene inactivation. A suggestive parallel comes from the paleontological record, which shows that in primitive vertebrates both jaws are essentially mirror images of each other. Our finding supports the notion that Dlx genes are homeotic genes associated with morphological novelty in the vertebrate lineage

Tbx1 and Bmp2 in the development of the ear, neural crest and pharyngeal system in mice

Dissertation presented to obtain the Ph.D degree in BiologyDevelopment of the vertebrate head involves complex interactions between tissues derived from the three germ layers. Significantly, alterations in the development of this region of the embryo are often associated with a wide variety of human congenital birth defects. Some of them are inherited disorders such as Treacher Collins, Branchio-oto-renal and DiGeorge syndromes. During embryonic development, morphogenesis of the craniofacial area occurs sequentially with the formation of a variety of transient structures, which then undergo complex sequential reorganization to form the adult structures.(...

Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids

International audienceThe amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain unknown. Here we show that lower-to-upper jaw transformation induced by inactivation of the Endothelin1-Dlx5/6 cascade involving Goosecoid results in loss of the tympanic membrane in mouse, but causes duplication of the tympanic membrane in chicken. Detailed anatomical analysis indicates that the relative positions of the primary jaw joint and first pharyngeal pouch led to the coupling of tympanic membrane formation with the lower jaw in mammals, but with the upper jaw in diapsids. We propose that differences in connection and release by various pharyngeal skeletal elements resulted in structural diversity, leading to the acquisition of the tympanic membrane in two distinct manners during amniote evolution

Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body mass

<p>Abstract</p> <p>Background</p> <p>The H6 homeobox genes <it>Hmx1</it>, <it>Hmx2</it>, and <it>Hmx3 </it>(also known as <it>Nkx5-3</it>; <it>Nkx5-2 </it>and <it>Nkx5-1</it>, respectively), compose a family within the NKL subclass of the ANTP class of homeobox genes. Hmx gene family expression is mostly limited to sensory organs, branchial (pharyngeal) arches, and the rostral part of the central nervous system. Targeted mutation of either <it>Hmx2 </it>or <it>Hmx3 </it>in mice disrupts the vestibular system. These tandemly duplicated genes have functional overlap as indicated by the loss of the entire vestibular system in double mutants. Mutants have not been described for <it>Hmx1</it>, the most divergent of the family.</p> <p>Results</p> <p>Dumbo (<it>dmbo</it>) is a semi-lethal mouse mutation that was recovered in a forward genetic mutagenesis screen. Mutants exhibit enlarged ear pinnae with a distinctive ventrolateral shift. Here, we report on the basis of this phenotype and other abnormalities in the mutant, and identify the causative mutation as being an allele of <it>Hmx1</it>. Examination of dumbo skulls revealed only subtle changes in cranial bone morphology, namely hyperplasia of the gonial bone and irregularities along the caudal border of the squamous temporal bone. Other nearby otic structures were unaffected. The semilethality of <it>dmbo/dmbo </it>mice was found to be ~40%, occured perinatally, and was associated with exencephaly. Surviving mutants of both sexes exhibited reduced body mass from ~3 days postpartum onwards. Most dumbo adults were microphthalmic. Recombinant animals and specific deletion-bearing mice were used to map the <it>dumbo </it>mutation to a 1.8 Mb region on Chromosome 5. DNA sequencing of genes in this region revealed a nonsense mutation in the first exon of H6 Homeobox 1 (<it>Hmx1</it>; also <it>Nkx5-3</it>). An independent spontaneous allele called misplaced ears (<it>mpe</it>) was also identified, confirming <it>Hmx1 </it>as the responsible mutant gene.</p> <p>Conclusion</p> <p>The divergence of <it>Hmx1 </it>from its paralogs is reflected by different and diverse developmental roles exclusive of vestibular involvement. Additionally, these mutant <it>Hmx1 </it>alleles represent the first mouse models of a recently-discovered Oculo-Auricular syndrome caused by mutation of the orthologous human gene.</p

Competence, specification and commitment in otic placode induction

The inner ear is induced from cranial ectoderm adjacent to the hindbrain. Despite almost a century of study, the molecular mechanisms of inner ear induction remain obscure. We have identified four genes expressed very early in the anlage of the inner ear, the otic placode. Pax-2, Sox-3, BMP-7 and Notch are all expressed in placodal ectoderm from the 4-5 somite stage (ss) onwards, well before the otic placode becomes morphologically visible at the 12-14ss. We have used these four molecular markers to show that cranial ectoderm becomes specified to form the otic placode at the 4-6ss, and that this ectoderm is committed to a placodal fate by the 10ss. We also demonstrate that much of the embryonic ectoderm is competent to generate an otic placode if taken at a sufficiently early age. We have mapped the location of otic placode-inducing activity along the rostrocaudal axis of the embryo, and have determined that this activity persists at least until the 10ss. Use of the four molecular otic placode markers suggests that induction of the otic placode in birds occurs earlier than previously thought, and proceeds in a series of steps that are independently regulated