Abstract
Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of invivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone invivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease.
Highlights
Cranial placodes give rise to cells of the sensory organs, including the optic lens, the nasal epithelium, otic structures, the adenohypophysis, and a subset of cranial nerves such as the trigeminal ganglia
Sensory placodes are formed at the interface of the non-neural ectoderm and neural plate, surrounding the anterior portion of the future central nervous system (CNS) (Figure S1A)
De-repression of endogenous Bone Morphogenetic Protein (BMP) signaling induces placode at the expense of neuroectoderm
Summary
Cranial placodes give rise to cells of the sensory organs, including the optic lens, the nasal epithelium, otic structures, the adenohypophysis, and a subset of cranial nerves such as the trigeminal ganglia. Cranial placode development has been characterized in model organisms, including the frog, zebrafish, chicken and to a lesser extent, the mouse (Baker and Bronner-Fraser, 2001; Bhattacharyya and Bronner-Fraser, 2004; Schlosser, 2006). Over the last few years, protocols have been developed for directing the fate of hESCs into specific cell lineages. The derivation of CNS cells was among the first hESC differentiation protocols developed in the field (Reubinoff et al, 2001; Zhang et al, 2001). In contrast to the successful derivation and application of defined CNS and NC derived cell types, there has been limited success on modeling cranial placode development in hPSCs
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