An Integrated Perspective of Evolution and Development: From Genes to Function to Ear, Lateral Line and Electroreception
Round 1
Reviewer 1 Report
In this article, Fritzsch reviews the development and evolution of lateral line, electroreception and inner ear sensory organs. The introduction describes the comparative approach used to examine patterns of gene expression in key animal species. Section 2 describes genes that are important for the development of neurons that connect the different sensory organs to the brain. Section 3 describes the morphogenetic changes that lead to the formation of the brainstem regions that connect to sensory organs. Section 4 describes genes that are involved in the differentiation of receptor cells. Overall the article summarizes a vast range of literature and provides an integrated view that will be of interest to a broad audience.
Following are some suggestions to improve the manuscript:
Throughout the abstract and the article, different genes are discussed. On line 19, downstream proteins are mentioned. Please clarify what types of proteins the author is referring to.
Figures need to be revised as follows:
Figure 1. The labels DC, CM and PC in A" are not visible in the figure.
Figure 1 legend:
Line 67, "aLL, pLL" should be "LL".
Line 67, "electrorector" should be "electroreceptor".
Line 71, "ends" should be "end".
Line 76, delete "ELL; electroreceptor lateral line neurons"
Not defined in Figure 1 legend: CB, SC, AVCN, DCN
Figure 2. A comparison between three animal groups is shown. The labels in the figure are not clear. Does "No Atoh" refers to lack of data on bHLH transcription factor expression? The legend seems to describe the cartoons on the left side of the figure, but what about the cartoons on the right side of the figure? What is the difference between Atoh and Atoh1? What is the difference between Neurog and Neurog1? CP needs to be defined in the legend of the figure.
Figure 5. "Mechanosensory hair cells evolve from single cells" should be "Mechanosensory hair cells evolve from single cell organisms".
Other editing suggestions:
Line 39, delete "ago" after Mya.
Line 41, "resembles" should be "resemble".
Line 48, "input that partially" should be "inputs that are partially".
Line 91, "connects" should be "connect".
Line 99, "its" should be "their".
Line 103, delete "that", delete "a", delete "that is expressed".
Line 108, delete "that innervate".
Line 116, delete "neurons in the", replace "but allow develop some" with "and partial loss of".
Line 121, delete "are".
Lines 154 to 159, this part is confusing. I suggest to rewrite it to clarify what the author wants to say.
Line 166, "cycles" should be "cycle".
Line 171, "projection" should be "projections".
Line 190, "ends neurons" should be "ends proliferation".
Line 202, "projection" should be "projections", delete "on".
Line 220, "has" should be "have".
Line 221, "Latera" should be "Lateral"; "projection" should be "projections".
Line 223, "show" should be "shows".
Line 228, "particularly" should be "particular"; "form" should be "formed'.
Line 230, "forming" should be "forms".
Lines 230-232, if a posterior canal does not form how can the connection occur?, please clarify.
Line 239, delete ", and"
Line 250, delete "a"
Line 256, "depends at least two" should be "depend at least on two".
Line 278, "cords" should be "cord".
Line 289, delete "set of".
Line 293, delete "interaction".
Line 300, "downregulation" should be "downregulated"; "but is" should be "through".
Line 308, delete "is"
Line 339, "electrorector" should be "electroreceptor".
Lines 377-381, it is not clear what the author wants to say about the relationship between hair cell orientation and innervation. Please clarify.
Line 382, "neuromasts" should be "neuromast".
Line 451, "centrally" should be "central".
Author Response
Dear reviewer,
thank you for the positive input. Please find attached the corrections (in red).
Throughout the abstract and the article, different genes are discussed. On line 19, downstream proteins are mentioned. Please clarify what types of proteins the author is referring to.
Proteins are highly expressed in developing hair cells and depend on their function. I have rephrased that section.
Figures need to be revised as follows:
Figure 1. The labels DC, CM and PC in A" are not visible in the figure.
Thank you, we have now changed the images in bold and changed CM in white
Figure 1 legend:
Line 67, "aLL, pLL" should be "LL".
Line 67, "electrorector" should be "electroreceptor".
Line 71, "ends" should be "end".
Line 76, delete "ELL; electroreceptor lateral line neurons"
Not defined in Figure 1 legend: CB, SC, AVCN, DCN
We changed aLL/pLL to LL, changed to ‘electroreceptor’, changed to ‘end’ , delete ‘ELL’ and added CB, SC, AVCN,DCN
Figure 2. A comparison between three animal groups is shown. The labels in the figure are not clear. Does "No Atoh" refers to lack of data on bHLH transcription factor expression? The legend seems to describe the cartoons on the left side of the figure, but what about the cartoons on the right side of the figure? What is the difference between Atoh and Atoh1? What is the difference between Neurog and Neurog1? CP needs to be defined in the legend of the figure.
Thank you, we have updated the description by adding more information. Atoh/Atoh1 and Neurog/Neurog1/2 are multiplications of vertebrate genes. CP is added now.
Figure 5. "Mechanosensory hair cells evolve from single cells" should be "Mechanosensory hair cells evolve from single cell organisms".
‘cell organisms’ is now added.
Other editing suggestions:
Line 39, delete "ago" after Mya.
Line 41, "resembles" should be "resemble".
Line 48, "input that partially" should be "inputs that are partially".
Line 91, "connects" should be "connect".
Changes are updated
Line 99, "its" should be "their".
Line 103, delete "that", delete "a", delete "that is expressed".
Line 108, delete "that innervate".
Line 116, delete "neurons in the", replace "but allow develop some" with "and partial loss of".
Line 121, delete "are".
Changes are updated
Lines 154 to 159, this part is confusing. I suggest to rewrite it to clarify what the author wants to say.
Part is removed and rephrased the remainder part.
Line 166, "cycles" should be "cycle".
Line 171, "projection" should be "projections".
Line 190, "ends neurons" should be "ends proliferation".
Line 202, "projection" should be "projections", delete "on".
Line 220, "has" should be "have".
Line 221, "Latera" should be "Lateral"; "projection" should be "projections".
Line 223, "show" should be "shows".
Line 228, "particularly" should be "particular"; "form" should be "formed'.
Line 230, "forming" should be "forms".
Lines 230-232, if a posterior canal does not form how can the connection occur?, please clarify.
PC is forming initially but degenerates later (see details)
Line 239, delete ", and"
Line 250, delete "a"
Line 256, "depends at least two" should be "depend at least on two".
Line 278, "cords" should be "cord".
Line 289, delete "set of".
Line 293, delete "interaction".
Line 300, "downregulation" should be "downregulated"; "but is" should be "through".
Line 308, delete "is"
Line 339, "electrorector" should be "electroreceptor".
Lines 377-381, it is not clear what the author wants to say about the relationship between hair cell orientation and innervation. Please clarify.
I have rephrased this section: A distinct pattern of the utricle and saccule have a separate innervation from the cerebellum to reach out one polarity (Fig. 5D) and receives a descending branch of the caudal vestibular neurons [21,134,204] to end up in a different innervation (Fig. 5D). I hope it is clear now?
Line 382, "neuromasts" should be "neuromast".
Line 451, "centrally" should be "central".
Thank you for the work, all changes are now taken care.
Reviewer 2 Report
An evolutionary perspective on vestibular nuclei and hair cells is presented by Fritzsch. He speculates that sensory systems (vestibular, lateral line, electroreception, auditory) are unique to project exclusively to the brainstem of vertebrates. This represents and hair cells' integrated perspective is presented to understand the gain and loss of different sensory systems. A common origin of hair cells depends on Eya1, Sox2, and Atoh1genetic background that generates the mechanosensory cells. Downstream are proteins that define the polarity of hair cells in the ear and lateral line, except electroreception that has no polarity. The lateral line and ear have a unique connection of stereocilia that requires Tmc1/2 to allow to perceive mechanosensory input whereas electroreception is in part unknown. All hair cells function by exciting via ribbons to activate neurons in that specific area, in comparison to the spinal cord, certain gains and losses of domains are to be clarified.
For example, another unique step is driven by an apparent Ptf1a duplication in the brainstem. Central projections of the ear might depend on the brainstem. The central projection has been described in various vertebrates to show the projection of the vestibular, lateral line, electroreception, and the cochlea. Three sets of central projection are known in vertebrates that develop a loss of all lateral lines .
Vestibular neurons project dorsally in the hindbrain in control and Lmx1a/b DKO mice, according to Fritzsch develop first the trigeminal and epibranchial neurons and central projection as shown in several figures.
followed, in sequence, vestibular, lateral line, and electroception, if present
A different developmental pattern exists in neuronal proliferation: nearly all neurons continue proliferation for a long time or lifetime whereas mammals have an early production of neurons that ends neurons very early. One would like to know what the connexion of such neurons with archi, paleo, and neo-cerebellum is through evolution, but the cerebellar connections are not dealt with, and the different contributions of the roof plate and the floor plate also remain largely unknown.
The basal plate contains efferent neurons that send axons to peripheral neurons. The alar plate contains neurons that receive input from either myelencephalon or peripheral afferents; maybe a comment on cerebellum evolution is needed. It is of interest the notion that the brainstem derives from the spinal cord, alar plate and basal plate have different contributions, we know that actively, the roof plate and the floor plate are involved: an evolutionary perspective is needed also for these structures.
Author Response
Dear reviewer,
thank you for the paper. I have added a few sentences (in red).
A different developmental pattern exists in neuronal proliferation: nearly all neurons continue proliferation for a long time or lifetime whereas mammals have an early production of neurons that ends neurons very early. One would like to know what the connexion of such neurons with archi, paleo, and neo-cerebellum is through evolution, but the cerebellar connections are not dealt with, and the different contributions of the roof plate and the floor plate also remain largely unknown.
Thank you for the comment. We are aware of the higher order projections that are clear in the auditory and vestibular system for which we have a limited connection for the lateral line and electroreceptions. We have added a sentence to highlight the higher projections.
The basal plate contains efferent neurons that send axons to peripheral neurons. The alar plate contains neurons that receive input from either myelencephalon or peripheral afferents; maybe a comment on cerebellum evolution is needed. It is of interest the notion that the brainstem derives from the spinal cord, alar plate and basal plate have different contributions, we know that actively, the roof plate and the floor plate are involved: an evolutionary perspective is needed also for these structures.
Thank you, we have added a sentence on the efferent system and provide a limited information to the cerebellum.
Round 2
Reviewer 2 Report
No further comments
Author Response
Thank your for your comments.
Bernd
