Drosophila- neurogenesis Flashcards
(13 cards)
whats Neurogenesis in Drosophila
-happens because of Homology/analogy to Vertebrate neurogenesis
-applying genetic methods in this organism has given us a detailed molecular understanding of their formation, and very similar principle are used in vertebrates.
how does the mesoderm give rise to neurones
-When the mesoderm invaginates to form internal structure of the embryo the neuroectoderm comes to lie ventrally….this will give rise to neurons
where does the neural tube develop in vertebrates
-dorsal side
whats inverted in arthropods and vertebrates
-D/V axis
-In the idealized arthropod, a circulatory system developed at the dorsal side whereas the nerve cord was located ventrally.
-In vertebrates it was the opposite the heart and the vascular system derived from a ventral position whereas the brain and nerve cord form ventrally
-A bone morphogenetic protein (BMP) / decapentaplegic signal (Dpp) signal
-BMP/Dpp is
=important for patterning DORSAL in Drosophila
=important for patterning VENTRAL in vertebrates
where does the inversion happen
-happened in the lineage leading to the chordates/vertebrates, after the echinoderms split off
homologous genes
-Although the genes have different names in vertebrates; if you flip over a fly you can directly match the genes up that define such domains in both organisms
-Different domains in the neural region can be defined by expression of genes in a precise bilateral pattern vnd at the midline and ind and msh more laterally
whats neurogenesis
-Not all cells in the fly neuroectoderm will become neurons some will remain ectodermal
-Single Neuronal cells are selected from a group of ~ equivalent cells: a PRONEURAL CLUSTER
-This process uses a highly important patterning mechanism that you will also come across in mouse/human:
=> LATERAL INHIBITION
whats lateral inhibition
-The Achaete/Scute genes
set up a cluster…
They are called
proneural genes
-The Notch/Delta
signaling pathway ensures selection of a single cell out of the cluster
-For neurogenesis the cluster of equivalent cells is set up by the Achaete Scute genes..this is why they are called Pro-Neural genes. Within this cluster a selection process is initiated using a cell to cell signaling pathway that is best known as the NOTCH/DELTA pathway
lateral inhibition pathway
-proneural genes promote Delta expression
-Delta is a transmembrane ligand , this means it is stuck in the membrane and can only act on cells that are direct neighbours.
-Here it specifically binds and activates the Notch receptor.
-No cell is really EXACTLY the same therefore there will be small differences in the level of delta that a cell expresses…
-A strong Notch signal will
downregulate Achaete/Scute
-As a result the small difference in
Achaete/Scute expression will
become amplified
-High and continuous achaete/scute
Expression activates Neural genes
-The ”losing cell” reverts to epidermal fate
what happens once a neuroblast is selected in lateral inhibition
-it will start to generate a number of Neuronal cells and Glial cells. The glial cells can be considered neuronal support cells.
-Also here the precise developmental process is interesting to consider becauses similar things happen in various different tissues and organisms, including human.
-The process is assymmetric cell division. So just like Lateral Inhibition it is a really basic developmental principle.
-So when the actual neuroblast has been selected via lateral inhibition, the cell will drop down from the lumen into the interior of the embryo.
-At this point it is important to mention that all cells of the drosophila epidermis have an inherent polarity…The cells “know” what is inside and outside.
-This is determined by having different proteins associated with the membrane that is in contact with the outside as compared to the inside.
-This type of cellular polarity is called APICO-BASAL polarity and this is something you will a come across more often in your course. The neuroblasts will remember this polarity.
After selection of the Neuroblast, it will generate a number of Neuronal and Glial cells, in a very stereotypic manner
-The “memory” consists of a localized
protein complex. Bazooka (=Par3 in mammals) and Insc/Pins are a part of this.
-The protein complex directs the localization of
proteins and certain RNAs on the opposite side of the cell, “Numb” is an important part of this
-The complex also orients the mitotic spindle, which determines the plane of division.
-As a result two cells are formed that are DIFFERENT
-One of them is the Neuroblast that will act like a stem cell and will continue to make differenting cells. The other cell that received the complex containing Numb will become a ganglion mother cell.
when are the sensory organs of adult flies formed
-during pupation in a quite similar manner. These are also formed from proneural clusters that express achaete scute that can already be seen in the imaginal discs as is illustrated here
-These sensory organs are formed from a single cell, the sensory organ precursor that will give rise to four cells. In this case the process is modified and the cell remains IN the epithelium and the division also occurs in this plane..
-Numb is also important in the next division, the cell that receives numb will differentiate as the sensory neuron
-It may be important to point out that the process is similar but not an exact copy of embryonic neurogenesis. In neuroblasts Numb is localized on the opposite side from Pins protein.
mammals the par3
-mammals the Par3- asymmetric cell division mechanism is also operative.
-In the cortex of a developing mouse neural stem cells have an unusual elongated shape, spanning the entire neural layer.Just before cell division the nucleus of these cells moves inward, so the “inside surface of the brain next to the brain ventricle. It is known that also here that if the division is asymmetric to from a differentiated neuron Par3 localization is towards the Stem cell…as was the case in drosophila
