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Recent studies have tried to answer important questions of what distinguishes the embryonic spatial 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, this can imply that spatial and temporal patterning could be very similar or even be equivalent. The hunchback gene has long been known for its essential role in spatial patterning in the Drosophila. In this essay I'm going to attempt to discuss how transcriptions factor such as hunchback can be involved spatially in invertebrate such as the drosophila. Moreover, I will try to explain the importance of temporal transcriptions factors and whether it is possible to separate out the difference between spatial and temporal transcriptions factors.
Irish et al (2001) studied the transcription factors involved in the formation of the anterior-posterior axis in the drosophila body plan. In the normal development of the drosophila embryo depended on the activity of the maternal determinants found at both ends of the egg. These activities defined the polarity of the anterior-posterior axis and the spatial domains of expression of the gap genes that control the steps in segmentation. However, mutation in these maternal posterior group genes resulted in embryos lacking all abdominal segments. Further studies suggested that the nanos gene acted as the abdominal determinant while other posterior group genes appear to be needed for the appropriate localisation of the nano signal. Additionally, when the nano gene were removed, it was possible to produce a viable fertile drosophila by eliminating hunchback gene. Vivian Irish (2001) concluded that this is due to how the nanos gene functions. The nanos act by repressing the activity of hunchback in the posterior of the egg. However, this raises an important issue, why have nanos and hunchback genes been conserved over time if both are not required for a viable drosophila. It may be that there was once a mechanism that was essential which required the nano and hunchback gene but are no longer needed (Irish et al 1989) or nanos and hunchback are involved in a different mechanism other than patterning spatial events.
However, recent studies have shown that Hunchback acts as a temporal transcription factor regulating temporal neuroblast identity (Lin et al, 2003). 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 (Isshiki et al, 2001). 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 normal development, each cell in the embryo needs to adopt the correct spatial and temporal identity. The first-born ganglion mother cells always express hunchback, and the second-born ganglion mother cells always express kruppel.
In the past it was thought that these transcription factor code for cell type identity. However, studies have shown this is not the case, for example, Hb+ progeny are all early born but can differentiate into interneurons, motor neurons or glia depending on the parental neuroblasts, there cell type fate was not determined by hunchback gene. This is also true for kr+ progeny and other known temporal transcription factors (Isshiki et al, 2001). Mutations in temporal transcription factors cause mis-expression of cell fate progeny, such that progeny are inappropriately skipped or over-expressed relative to normal development. 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-/-). For example, hunchback is necessary and sufficient for normal first born ganglion mother cell development but not later born cell fates. Using recent research a model was proposed for drosophila that is each gene activates the next gene and represses the "next plus one" gene. This suggests that hunch back may have been conserved over time in the drosophila to act as a temporal transcription factor than pattern spatial identity. Moreover, research in hunchback over-expression causes replication of first-born fates, this confirms previous loss-of-function studies. Overall, 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 other invertebrates such as C. Elegans, where gene lin-41 causes seam cells to incorrectly 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, hunchback homologs have now been shown to control temporal patterning in different line of descents, emphasises the 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. 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.
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 (Zhu et al, 2006).
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 seem 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 (Britanova et al, 2008). From this is possible to tell that there is a complex mechanism involved in the development of central nervous system in an organism from the neuroblasts to neurons, it involves many different transcription factors. So far our knowledge in this field is still at early stage. But further research, it will become more clear of the importance of temporal transcription factor and differentiate between spatial and temporal transcription factors as more evidence emerge. Moreover, there is only limited evidence that the factors involved in insect neuronal temporal specification play conserved roles in vertebrates.
So far studies have shown 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. This may suggest that the role of temporal transcription factor does play important roles in patterning the development of an organism but more evidence is required to fully understand the complexity.
Although many of the temporal factors themselves might not be functionally conserved in the vertebrates, evolutionary comparisons led us 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 been 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 and glial progeny had now been well understood. The importance of temporal specification during neurogenesis has been recognised recently and has been shown on drosophila and vertebrates alike.