Recent studies have tried to answer important questions of what distinguishes the embryonic spatial roles and temporal roles of transcription factors such as hunchback and kruppel. Some researchers now believe that there could be genetic interactions between the spatial and temporal roles that have been conserved over time. Hunchback has long been known for its essential role in spatial patterning in the Drosophila.
The development of the body plan in the drosophila embryo depends on the activity of the maternal determinants found at both ends of the egg. These activities define the polarity of the anterior-posterior axis and the spatial domains of expression of the gap genes control the steps in segmentation. Mutation in these maternal posterior group genes results in embryos lacking all abdominal segments. Studies suggest that the nanos gene acts as the abdominal determinant while other posterior group genes appear to be needed for the appropriate localisation of the nano signal. Furthermore, when the nano gene is removed, it is possible to produce a viable fertile drosophila by eliminating hunchback gene. Vivian Irish (2001) suggested that this is due to the nanos gene function as nanos act by repressing the activity of hunchback in the posterior of the egg. However, there is no reason to suggest why nanos and hunchback have been conserved over time as without them a fertile drosophila is possible. It may be that there was once a mechanism that was essential which required the nano and hunchback gene but are no longer needed (6).
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However, recent studies have shown that Hunchback acts as a temporal transcription factor regulating temporal neuroblast identity (7). In Drosophila, multipotent neuroblasts express a sequence of progenitor transcription factors which regulates the postmitotic transcription factors that give rise to neuronal and glial temporal identities. Each neuroblasts divide asymmetrically to form a neuroblasts and a ganglion mother cell. These neuroblasts create four classes of ganglion mother cells, derived from four neuroblast divisions (2). The four known temporal transcription factors are Hunchback (Hb), Kruppel (Kr), Pdm and Castor (Cas). These progenitor temporal transcription factors are transiently expressed and are necessary to give temporal identity in postmitotic daughter cells. Each progenitor temporal transcription factors is switched on at specific time window so a certain type of progeny is born.
For development, each cell in the developing organism needs to adopt the correct spatial and temporal identity. The first-born ganglion mother cells express hunchback, and the second-born ganglion mother cells express Kruppel. this can not mean that these transcription factor code for cell type identity as for example, since Hb+ progeny are all early born but can differentiate as interneurons, motor neurons or glia depending on the parental neuroblasts. This is also true for kr+ progeny. They all show the same sequence transition pattern. Mutations in temporal transcription factors cause mis-expression of cell fate progeny, such that stage-specific progeny are inappropriately skipped or over-expressed relative to wild-type. For example, loss-of-function mutations in the drosophila leads to skipping of temporal identity (Hb-/-, Kr-/-, Pdm-/-) or stalled temporal series progression (Pdm-dependent Cas-/-). E.g. Hunchback is necessary and sufficient for normal GMC-1 development but not later born cell fates. A model has been proposed for drosophila that is each gene activates the next gene and represses the â€œnext plus oneâ€Â gene. In contrast, hunchback over-expression causes replication of first-born fates. Recent studies on Loss-/gain-of-function show that progenitor temporal transcription factor is necessary and sufficient to give temporal identity. This is also true for C. Elegans, where gene lin-41 cause seam cells to inappropriately adopt adult fates in the fourth larval stage and over expression of lin-41 causes the seam cells to repeat larval fates at the adult stage (Slack et al., 2000). This suggests that the lin-41 gene encodes a key developmental switch that represses adult seam cell fates until their proper expression time. In C. Elegans, we have similarly observed precocious expression of later fates in hbl-1 mutants. Hunchback homologs have now been shown to control temporal patterning in different phyla, underscoring a potential evolutionarily conserved role for hunchback family members in controlling temporal identity.
The transition from one progenitor temporal transcription factors to the next involves switching factors. Switching factors regulate temporal identity transitions in neuroblasts, turning on and off different progenitor temporal transcription factors at specific times. Prolonged periods of an early identity causes overproduction of early-born cell types, at the expense of other later-born cell types. In Drosophila, the known switching factors are Svp and Cas (re-word. Wt yu tryna say?). In vertebrates, Coup-TFI and Coup-TFII are required for switching from neurogenesis to gliogenesis. Double knockdown of Coup-TFI and II in neural progenitor cells caused sustained neurogenesis and defective gliogenesis in the developing mouse forebrain.
Always on Time
Marked to Standard
Postmitotic temporal transcription factors are expressed and required in postmitotic neurons and glia to give their temporal identity. Post-transcriptional regulation is used to control gradient expression of Chinmo. Neurons born at early developmental stages contain chinmo and then during late larval stages produce Broad-Complex. Embryonic Cas-activity permanently switches the expression of Grainyhead on and Dichaete off (14).
In vertebrate, pyramidal neurons of the neo-cortex can be subdivided into two major groups: deep- layer neurons and upper-layer neurons. Postmitotic projection neurons of the different layers express different combinations of Sox5, Ctip2+ and Satb2. When Sox5 is inactivated the sub-plate neurons it seems to be replaced by ectopic Ctip2+ neurons. Satb2 is a gene that is expressed predominantly in young upper-layer neurons. Inactivation of Satb2+ leads neurons to acquire an earlier Ctip2+ identity. Satb2 and Ctip2 control mutually exclusive genetic programs of upper-layer and deep-layer cell-type specification (13).
As yet, however, there is only limited evidence that the factors involved in insect neuronal temporal specification play conserved roles in vertebrates.
In most rhombomeres of normal mouse and chick hindbrains, there is a switch in the visceral motor neurons to serotonergic neurons. Ventral progenitors first express Phox2b and then Foxa2. Absence of Foxa2, results in visceral motor neurons generation being prolonged and serotonergic neuronal production blocked, this is also true for Phox2b. However, in rhombomeres 4, it is different as transition is suppressed and visceral motor production is prolonged because HoxB1 maintains expression of Phox2B and suppresses Foxa2.
Although many of the temporal factors themselves might not be functionally conserved in vertebrates, evolutionary comparisons led to hypothesise that there is a common underlying regulatory framework. Spatial and temporal patterning may share certain features. Their functions of key genes and their mechanisms of regulating expression are preserved.
If spatial and temporal roles are different, hunchback function could have originally evolved for spatial patterning but could have then been taken over by temporal patterning programs or vice versa. Alternatively, because spatial patterns reveal themselves during development for example, along the temporal axis, it is often difficult to separate temporal and spatial patterning. For example, studies by Gamberi et al (2002) suggested that temporal changes in bicoid gene expression during embryogenesis in drosophila resulted in altered spatial patterns. This may suggests that spatial and temporal patterning programs could be mechanistically very similar and may even be equivalent.
Spatial patterning cues that regulate the properties of progenitors and their neuronal/glial progeny had now been well understood (Jessell, 2000; Skeath and Thor, 2003). The importance of temporal specification during neurogenesis has been recognised ever since it was first demonstrated that different types of neurons are born in a stereotypical order in the developing mammalian cerebral cortex (Berry et al., 1964).
Egger et al., 2008; Pearson and Doe, 2004). Qian et al., 2000; Shen et al., 2006).