Search

Foxg1 is a key regulator of the early development of the vertebrate forebrain and sensory organs. In this study, we describe for the first time three foxg1 paralogues in lamprey, representative of one of two basally diverged lineages of vertebrates—the agnathans. We also first describe three foxg1 genes in sterlet—representative of one of the evolutionarily ancient clades of gnathostomes. According to the analysis of local genomic synteny, three foxg1 genes of agnathans and gnathostomes have a common origin as a result of two rounds of genomic duplications in the early evolution of vertebrates. At the same time, it is difficult to reliably establish pairwise orthology between foxg1 genes of agnathans and gnathostomes based on the analysis of phylogeny and local genomic synteny, as well as our studies of the spatiotemporal expression of foxg1 genes in the river lamprey Lampetra fluviatilis and the sterlet Acipenser ruthenus. Thus, the appearance of three foxg1 paralogues in agnathans and gnathostomes could have occurred either as a result of two rounds of duplication of the vertebrate common ancestor genome (2R hypothesis) or as a result of the first common round followed by subsequent independent polyploidizations in two evolutionary lineages (1R hypothesis).

Neuronal development in the inner ear is initiated by expression of the proneural basic Helix-Loop-Helix (bHLH) transcription factor Neurogenin1 that specifies neuronal precursors in the otocyst. The initial specification of the neuroblasts within the otic epithelium is followed by the expression of an additional bHLH factor, Neurod1. Although NEUROD1 is essential for inner ear neuronal development, the different aspects of the temporal and spatial requirements of NEUROD1 for the inner ear and, mainly, for auditory neuron development are not fully understood. In this study, using Foxg1Cre for the early elimination of Neurod1 in the mouse otocyst, we showed that Neurod1 deletion results in a massive reduction of differentiating neurons in the otic ganglion at E10.5, and in the diminished vestibular and rudimental spiral ganglia at E13.5. Attenuated neuronal development was associated with reduced and disorganized sensory epithelia, formation of ectopic hair cells, and the shortened cochlea in the inner ear. Central projections of inner ear neurons with conditional Neurod1 deletion are reduced, unsegregated, disorganized, and interconnecting the vestibular and auditory systems. In line with decreased afferent input from auditory neurons, the volume of cochlear nuclei was reduced by 60% in Neurod1 mutant mice. Finally, our data demonstrate that early elimination of Neurod1 affects the neuronal lineage potential and alters the generation of inner ear neurons and cochlear afferents with a profound effect on the first auditory nuclei, the cochlear nuclei.

Coordination of craniofacial development involves an complex, intricate, genetically controlled and tightly regulated spatiotemporal series of reciprocal inductive and responsive interactions among the embryonic cephalic epithelia (both endodermal and ectodermal) and the cephalic mesenchyme — particularly the cranial neural crest (CNC). The coordinated regulation of these interactions is critical both ontogenetically and evolutionarily, and the clinical importance and mechanistic sensitivity to perturbation of this developmental system is reflected by the fact that one-third of all human congenital malformations affect the head and face. Here, we focus on one element of this elaborate process, apoptotic cell death, and its role in normal and abnormal craniofacial development. We highlight four themes in the temporospatial elaboration of craniofacial apoptosis during development, namely its occurrence at (1) positions of epithelial-epithelial apposition, (2) within intra-epithelial morphogenesis, (3) during epithelial compartmentalization, and (4) with CNC metameric organization. Using the genetic perturbation of Satb2, Pbx1/2, Fgf8, and Foxg1 as exemplars, we examine the role of apoptosis in the elaboration of jaw modules, the evolution and elaboration of the lambdoidal junction, the developmental integration at the mandibular arch hinge, and the control of upper jaw identity, patterning and development. Lastly, we posit that apoptosis uniquely acts during craniofacial development to control patterning cues emanating from core organizing centres.

Sensorineural deafness is mainly caused by damage to the tissues of the inner ear, and hearing impairment has become an increasingly serious global health problem. When the inner ear is abnormally developed or is damaged by inflammation, ototoxic drugs, or blood supply disorders, auditory signal transmission is inhibited resulting in hearing loss. Forkhead box G1 (FoxG1) is an important nuclear transcriptional regulator, which is related to the differentiation, proliferation, development, and survival of cells in the brain, telencephalon, inner ear, and other tissues. Previous studies have shown that when FoxG1 is abnormally expressed, the development and function of inner ear hair cells is impaired. This review discusses the role and regulatory mechanism of FoxG1 in inner ear tissue from various aspects – such as the effect on inner ear development, the maintenance of inner ear structure and function, and its role in the inner ear when subjected to various stimulations or injuries – in order to explain the potential significance of FoxG1 as a new target for the treatment of hearing loss.

Foxg1 is a key regulator of the early development of the vertebrate forebrain and sensory organs. In this study, we describe for the first time three foxg1 paralogues in lamprey, representative of one of two basally diverged lineages of vertebrates-the agnathans. We also first describe three foxg1 genes in sterlet-representative of one of the evolutionarily ancient clades of gnathostomes. According to the analysis of local genomic synteny, three foxg1 genes of agnathans and gnathostomes have a common origin as a result of two rounds of genomic duplications in the early evolution of vertebrates. At the same time, it is difficult to reliably establish pairwise orthology between foxg1 genes of agnathans and gnathostomes based on the analysis of phylogeny and local genomic synteny, as well as our studies of the spatiotemporal expression of foxg1 genes in the river lamprey Lampetra fluviatilis and the sterlet Acipenser ruthenus . Thus, the appearance of three foxg1 paralogues in agnathans and gnathostomes could have occurred either as a result of two rounds of duplication of the vertebrate common ancestor genome (2R hypothesis) or as a result of the first common round followed by subsequent independent polyploidizations in two evolutionary lineages (1R hypothesis)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ermakova, Kucheryavyy, Mugue, Mischenko, Zaraisky and Bayramov.)

Neuronal development in the inner ear is initiated by expression of the proneural basic Helix-Loop-Helix (bHLH) transcription factor Neurogenin1 that specifies neuronal precursors in the otocyst. The initial specification of the neuroblasts within the otic epithelium is followed by the expression of an additional bHLH factor, Neurod1. Although NEUROD1 is essential for inner ear neuronal development, the different aspects of the temporal and spatial requirements of NEUROD1 for the inner ear and, mainly, for auditory neuron development are not fully understood. In this study, using Foxg1 Cre for the early elimination of Neurod1 in the mouse otocyst, we showed that Neurod1 deletion results in a massive reduction of differentiating neurons in the otic ganglion at E10.5, and in the diminished vestibular and rudimental spiral ganglia at E13.5. Attenuated neuronal development was associated with reduced and disorganized sensory epithelia, formation of ectopic hair cells, and the shortened cochlea in the inner ear. Central projections of inner ear neurons with conditional Neurod1 deletion are reduced, unsegregated, disorganized, and interconnecting the vestibular and auditory systems. In line with decreased afferent input from auditory neurons, the volume of cochlear nuclei was reduced by 60% in Neurod1 mutant mice. Finally, our data demonstrate that early elimination of Neurod1 affects the neuronal lineage potential and alters the generation of inner ear neurons and cochlear afferents with a profound effect on the first auditory nuclei, the cochlear nuclei., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Filova, Bohuslavova, Tavakoli, Yamoah, Fritzsch and Pavlinkova.)

Coordination of craniofacial development involves an complex, intricate, genetically controlled and tightly regulated spatiotemporal series of reciprocal inductive and responsive interactions among the embryonic cephalic epithelia (both endodermal and ectodermal) and the cephalic mesenchyme - particularly the cranial neural crest (CNC). The coordinated regulation of these interactions is critical both ontogenetically and evolutionarily, and the clinical importance and mechanistic sensitivity to perturbation of this developmental system is reflected by the fact that one-third of all human congenital malformations affect the head and face. Here, we focus on one element of this elaborate process, apoptotic cell death, and its role in normal and abnormal craniofacial development. We highlight four themes in the temporospatial elaboration of craniofacial apoptosis during development, namely its occurrence at (1) positions of epithelial-epithelial apposition, (2) within intra-epithelial morphogenesis, (3) during epithelial compartmentalization, and (4) with CNC metameric organization. Using the genetic perturbation of Satb2 , Pbx1/2 , Fgf8 , and Foxg1 as exemplars, we examine the role of apoptosis in the elaboration of jaw modules, the evolution and elaboration of the lambdoidal junction, the developmental integration at the mandibular arch hinge, and the control of upper jaw identity, patterning and development. Lastly, we posit that apoptosis uniquely acts during craniofacial development to control patterning cues emanating from core organizing centres., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Compagnucci, Martinus, Griffin and Depew.)

Sensorineural deafness is mainly caused by damage to the tissues of the inner ear, and hearing impairment has become an increasingly serious global health problem. When the inner ear is abnormally developed or is damaged by inflammation, ototoxic drugs, or blood supply disorders, auditory signal transmission is inhibited resulting in hearing loss. Forkhead box G1 (FoxG1) is an important nuclear transcriptional regulator, which is related to the differentiation, proliferation, development, and survival of cells in the brain, telencephalon, inner ear, and other tissues. Previous studies have shown that when FoxG1 is abnormally expressed, the development and function of inner ear hair cells is impaired. This review discusses the role and regulatory mechanism of FoxG1 in inner ear tissue from various aspects - such as the effect on inner ear development, the maintenance of inner ear structure and function, and its role in the inner ear when subjected to various stimulations or injuries - in order to explain the potential significance of FoxG1 as a new target for the treatment of hearing loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Ding, Meng, Kong, He and Chai.)